Journal articles: 'Conserved RNA Structures'

1

Shepard, P. J., and K. J. Hertel. "Conserved RNA secondary structures promote alternative splicing." RNA 14, no. 8 (June 20, 2008): 1463–69. http://dx.doi.org/10.1261/rna.1069408.

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Kiening, Ochsenreiter, Hellinger, Rattei, Hofacker, and Frishman. "Conserved Secondary Structures in Viral mRNAs." Viruses 11, no. 5 (April 29, 2019): 401. http://dx.doi.org/10.3390/v11050401.

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RNA secondary structure in untranslated and protein coding regions has been shown to play an important role in regulatory processes and the viral replication cycle. While structures in non-coding regions have been investigated extensively, a thorough overview of the structural repertoire of protein coding mRNAs, especially for viruses, is lacking. Secondary structure prediction of large molecules, such as long mRNAs remains a challenging task, as the contingent of structures a sequence can theoretically fold into grows exponentially with sequence length. We applied a structure prediction pipeline to Viral Orthologous Groups that first identifies the local boundaries of potentially structured regions and subsequently predicts their functional importance. Using this procedure, the orthologous groups were split into structurally homogenous subgroups, which we call subVOGs. This is the first compilation of potentially functional conserved RNA structures in viral coding regions, covering the complete RefSeq viral database. We were able to recover structural elements from previous studies and discovered a variety of novel structured regions. The subVOGs are available through our web resource RNASIV (RNA structure in viruses; http://rnasiv.bio.wzw.tum.de).

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3

Witwer, C. "Conserved RNA secondary structures in Picornaviridae genomes." Nucleic Acids Research 29, no. 24 (December 15, 2001): 5079–89. http://dx.doi.org/10.1093/nar/29.24.5079.

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4

Thurner, Caroline, Christina Witwer, Ivo L. Hofacker, and Peter F. Stadler. "Conserved RNA secondary structures in Flaviviridae genomes." Journal of General Virology 85, no. 5 (May 1, 2004): 1113–24. http://dx.doi.org/10.1099/vir.0.19462-0.

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Presented here is a comprehensive computational survey of evolutionarily conserved secondary structure motifs in the genomic RNAs of the family Flaviviridae. This virus family consists of the three genera Flavivirus, Pestivirus and Hepacivirus and the group of GB virus C/hepatitis G virus with a currently uncertain taxonomic classification. Based on the control of replication and translation, two subgroups were considered separately: the genus Flavivirus, with its type I cap structure at the 5′ untranslated region (UTR) and a highly structured 3′ UTR, and the remaining three groups, which exhibit translation control by means of an internal ribosomal entry site (IRES) in the 5′ UTR and a much shorter less-structured 3′ UTR. The main findings of this survey are strong hints for the possibility of genome cyclization in hepatitis C virus and GB virus C/hepatitis G virus in addition to the flaviviruses; a surprisingly large number of conserved RNA motifs in the coding regions; and a lower level of detailed structural conservation in the IRES and 3′ UTR motifs than reported in the literature. An electronic atlas organizes the information on the more than 150 conserved, and therefore putatively functional, RNA secondary structure elements.

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5

Mironov, A. A. "New method to predict conserved RNA structures." Molecular Biology 41, no. 4 (August 2007): 642–49. http://dx.doi.org/10.1134/s0026893307040188.

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6

Hooks, Katarzyna B., and Sam Griffiths-Jones. "Conserved RNA structures in the non-canonical Hac1/Xbp1 intron." RNA Biology 8, no. 4 (July 2011): 552–56. http://dx.doi.org/10.4161/rna.8.4.15396.

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7

Freidhoff, Paul, and Michael F. Bruist. "In silico survey of the central conserved regions in viroids of the Pospiviroidae family for conserved asymmetric loop structures." RNA 25, no. 8 (May 23, 2019): 985–1003. http://dx.doi.org/10.1261/rna.070409.119.

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8

LE, SHU-YUN, JACOB V. MAIZEL, and KAIZHONG ZHANG. "FINDING CONSERVED WELL-ORDERED RNA STRUCTURES IN GENOMIC SEQUENCES." International Journal of Computational Intelligence and Applications 04, no. 04 (December 2004): 417–30. http://dx.doi.org/10.1142/s1469026804001409.

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Recent advances in RNA studies show that the well-ordered, structured RNAs perform a broad functions in various biological mechanisms. Included among these functions are regulations of gene expression at multiple levels by diversified ribozymes and various RNA regulatory elements. The discovered microRNAs (miRNAs) with a distinct stem-loops are a new class of RNA regulatory elements. The prediction of those well-ordered folding sequences (WFS) associated with the RNA regulatory elements in genomic sequences is very helpful for our understandings of RNA-based gene regulations. We present here a new computational method in searching for the conserved WFS in genomes. In the method, the WFS is assessed by a quantitative measure E diff that is defined as the difference of free energies between the computed optimal structure (OS) and its corresponding optimal restrained structure where all the previous base pairings in the OS are forbidden. From those WFS with high E diff scores, the conserved WFS is determined by computing the maximal similarity score (MSS) between the two compared structures. In practice, we first search for those distinct WFS with high statistical significance in genomic sequences and then seek for those conserved WFS with high MSS. The potential and implications of our discoveries in the genome of Caenorhabditis elegans are discussed.

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9

Asturias, F. J., Y. W. Jiang, L. C. Myers, C. M. Gustafsson, and R. D. Kornberg. "Conserved Structures of Mediator and RNA Polymerase II Holoenzyme." Science 283, no. 5404 (February 12, 1999): 985–87. http://dx.doi.org/10.1126/science.283.5404.985.

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10

Hofacker, I. L., P. F. Stadler, and R. R. Stocsits. "Conserved RNA secondary structures in viral genomes: a survey." Bioinformatics 20, no. 10 (July 1, 2004): 1495–99. http://dx.doi.org/10.1093/bioinformatics/bth108.

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11

Chen, Qingfeng, Yi-Ping Phoebe Chen, and Chengqi Zhang. "Interval-Based Similarity for Classifying Conserved RNA Secondary Structures." IEEE Intelligent Systems 31, no. 3 (May 2016): 78–85. http://dx.doi.org/10.1109/mis.2015.2.

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12

Fricke, Markus, Nadia Dünnes, Margarita Zayas, Ralf Bartenschlager, Michael Niepmann, and Manja Marz. "Conserved RNA secondary structures and long-range interactions in hepatitis C viruses." RNA 21, no. 7 (May 11, 2015): 1219–32. http://dx.doi.org/10.1261/rna.049338.114.

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13

Mauger, David M., Michael Golden, Daisuke Yamane, Sara Williford, Stanley M. Lemon, Darren P. Martin, and Kevin M. Weeks. "Functionally conserved architecture of hepatitis C virus RNA genomes." Proceedings of the National Academy of Sciences 112, no. 12 (March 9, 2015): 3692–97. http://dx.doi.org/10.1073/pnas.1416266112.

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Hepatitis C virus (HCV) infects over 170 million people worldwide and is a leading cause of liver disease and cancer. The virus has a 9,650-nt, single-stranded, messenger-sense RNA genome that is infectious as an independent entity. The RNA genome has evolved in response to complex selection pressures, including the need to maintain structures that facilitate replication and to avoid clearance by cell-intrinsic immune processes. Here we used high-throughput, single-nucleotide resolution information to generate and functionally test data-driven structural models for three diverse HCV RNA genomes. We identified, de novo, multiple regions of conserved RNA structure, including all previously characterized cis-acting regulatory elements and also multiple novel structures required for optimal viral fitness. Well-defined RNA structures in the central regions of HCV genomes appear to facilitate persistent infection by masking the genome from RNase L and double-stranded RNA-induced innate immune sensors. This work shows how structure-first comparative analysis of entire genomes of a pathogenic RNA virus enables comprehensive and concise identification of regulatory elements and emphasizes the extensive interrelationships among RNA genome structure, viral biology, and innate immune responses.

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14

Cunningham, Caylee, Joshua Imperatore, Ella Milback, Morgan Shine, Kendy A. Pellegrene, Patrick Lackey, Jeffrey D. Evanseck, and Mihaela-Rita Mihailescu. "Characterization of SARS-CoV-2 Conserved Elements’ Structures and their RNA-RNA Interactions." Biophysical Journal 120, no. 3 (February 2021): 313a. http://dx.doi.org/10.1016/j.bpj.2020.11.1983.

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15

Fricke, Markus, Nadia Dünnes, Margarita Zayas, Ralf Bartenschlager, Michael Niepmann, and Manja Marz. "Corrigendum: Conserved RNA secondary structures and long-range interactions in hepatitis C viruses." RNA 22, no. 10 (September 16, 2016): 1640.1. http://dx.doi.org/10.1261/rna.058123.116.

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16

VAN NUES, R. W. "Saccharomyces SRP RNA secondary structures: A conserved S-domain and extended Alu-domain." RNA 10, no. 1 (January 1, 2004): 75–89. http://dx.doi.org/10.1261/rna.5137904.

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17

Pervouchine, D. D., E. E. Khrameeva, M. Y. Pichugina, O. V. Nikolaienko, M. S. Gelfand, P. M. Rubtsov, and A. A. Mironov. "Evidence for widespread association of mammalian splicing and conserved long-range RNA structures." RNA 18, no. 1 (November 29, 2011): 1–15. http://dx.doi.org/10.1261/rna.029249.111.

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18

Burd, C., and G. Dreyfuss. "Conserved structures and diversity of functions of RNA-binding proteins." Science 265, no. 5172 (July 29, 1994): 615–21. http://dx.doi.org/10.1126/science.8036511.

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19

Seetin, Matthew G., and David H. Mathews. "TurboKnot: rapid prediction of conserved RNA secondary structures including pseudoknots." Bioinformatics 28, no. 6 (January 27, 2012): 792–98. http://dx.doi.org/10.1093/bioinformatics/bts044.

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20

Doose, Gero, and Dirk Metzler. "Bayesian sampling of evolutionarily conserved RNA secondary structures with pseudoknots." Bioinformatics 28, no. 17 (July 13, 2012): 2242–48. http://dx.doi.org/10.1093/bioinformatics/bts369.

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21

Coey, Aaron, Kevin Larsen, Joseph D. Puglisi, and Elisabetta Viani Puglisi. "Heterogeneous structures formed by conserved RNA sequences within the HIV reverse transcription initiation site." RNA 22, no. 11 (September 9, 2016): 1689–98. http://dx.doi.org/10.1261/rna.056804.116.

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22

LEONTIS, NEOCLES B., and ERIC WESTHOF. "Conserved geometrical base-pairing patterns in RNA." Quarterly Reviews of Biophysics 31, no. 4 (November 1998): 399–455. http://dx.doi.org/10.1017/s0033583599003479.

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1. INTRODUCTION 3992. DEFINITIONS 4013. CIS BASEPAIRS 4103.1 Cis Watson–Crick/Watson–Crick 4103.2 Wobble pairings 4113.3 Cis Watson–Crick/Hoogsteen pairings 4163.4 Bifurcated pairings 4173.5 Cis open and water-inserted 4214. TRANS BASEPAIRS 4234.1 Trans Watson–Crick/Watson–Crick 4234.2 Trans wobble pairs 4244.3 Trans Watson–Crick/Hoogsteen pairs 4244.4 Trans Hoogsteen/Hoogsteen pairs 4304.5 Trans bifurcated pairings 4325. SHALLOW-GROOVE PAIRINGS 4325.1 Hoogsteen/Shallow-groove pairs 4335.2 Watson–Crick/Shallow-groove pairings 4385.3 Shallow-groove/Shallow-groove pairings 4406. SIDE-BY-SIDE BASES 4467. DEFINING A LIBRARY OF ISOSTERIC PAIRINGS 4468. CONCLUSIONS 4519. ACKNOWLEDGEMENTS 45210. REFERENCES 452RNA molecules fold into a bewildering variety of complex 3D structures. Almost every new RNA structure obtained at high resolution reveals new, unanticipated structural motifs, which we are rarely able to predict at the current stage of our theoretical understanding. Even at the most basic level of specific RNA interactions – base-to-base pairing – new interactions continue to be uncovered as new structures appear. Compilations of possible non-canonical base-pairing geometries have been presented in previous reviews and monographs (Saenger, 1984; Tinoco, 1993). In these compilations, the guiding principle applied was the optimization of hydrogen-bonding. All possible pairs with two standard H-bonds were presented and these were organized according to symmetry or base type. However, many of the features of RNA base-pairing interactions that have been revealed by high-resolution crystallographic analysis could not have been anticipated and, therefore were not incorporated into these compilations. These will be described and classified in the present review. A recently presented approach for inferring basepair geometry from patterns of sequence variation (Gautheret & Gutell, 1997) relied on the 1984 compilation of basepairs (Saenger, 1984), and was extended to include all possible single H-bond combinations not subject to steric clashes. Another recent review may be consulted for a discussion of the NMR spectroscopy and thermodynamic effects of non-canonical (‘mismatched’) RNA basepairs on duplex stability (Limmer, 1997).

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23

Faro-Trindade, I., and P. R. Cook. "Transcription factories: structures conserved during differentiation and evolution." Biochemical Society Transactions 34, no. 6 (October 25, 2006): 1133–37. http://dx.doi.org/10.1042/bst0341133.

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Many cellular functions take place in discrete compartments, but our textbooks make little reference to any compartments involved in transcription. We review the evidence that active RNA polymerases and associated factors cluster into ‘factories’ that carry out many (perhaps all) of the functions required to generate mature transcripts. Clustering ensures high local concentrations and efficient interaction. Then, a gene must associate with the appropriate factory before it can be transcribed. Recent results show that the density and diameter of nucleoplasmic factories remain roughly constant as cells differentiate, despite large changes in the numbers of active polymerases and nucleoplasmic volumes.

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24

Somvanshi, Pallavi, and Prahlad Kishore Seth. "Predicted RNA secondary structures for the conserved regions in dengue virus." Bioinformation 3, no. 10 (July 27, 2009): 435–39. http://dx.doi.org/10.6026/97320630003435.

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25

Seemann, Stefan E., Aashiq H. Mirza, Claus Hansen, Claus H. Bang-Berthelsen, Christian Garde, Mikkel Christensen-Dalsgaard, Elfar Torarinsson, et al. "The identification and functional annotation of RNA structures conserved in vertebrates." Genome Research 27, no. 8 (May 9, 2017): 1371–83. http://dx.doi.org/10.1101/gr.208652.116.

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26

Khaladkar, Mugdha, Vandanaben Patel, Vivian Bellofatto, Jeffrey Wilusz, and Jason T. L. Wang. "Detecting conserved secondary structures in RNA molecules using constrained structural alignment." Computational Biology and Chemistry 32, no. 4 (August 2008): 264–72. http://dx.doi.org/10.1016/j.compbiolchem.2008.03.013.

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27

Lesnik, Elena A., Gary B. Fogel, Dana Weekes, Timothy J. Henderson, Harold B. Levene, Rangarajan Sampath, and David J. Ecker. "Identification of conserved regulatory RNA structures in prokaryotic metabolic pathway genes." Biosystems 80, no. 2 (May 2005): 145–54. http://dx.doi.org/10.1016/j.biosystems.2004.11.002.

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28

Huang, Liyu, Qingfeng Chen, Yongjie Li, and Cheng Luo. "Classifying Conserved RNA Secondary Structures With Pseudoknots by Vector-Edit Distance." IEEE Access 9 (2021): 32008–18. http://dx.doi.org/10.1109/access.2021.3058263.

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29

Allmansberger, Rudolf, Martin Bokranz, Lothar Kröckel, Jürgen Schallenberg, and Albrecht Klein. "Conserved gene structures and expression signals in methanogenic archaebacteria." Canadian Journal of Microbiology 35, no. 1 (January 1, 1989): 52–57. http://dx.doi.org/10.1139/m89-008.

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A comparative analysis of cotranscribed gene clusters comprising the structural genes mcrA, mcrB, mcrC, mcrD, and mcrG was carried out in three species of methanogens. mcrA, mcrB, and mcrG are the structural genes for the three subunits of methyl coenzyme M reductase, while the two other genes encode polypeptides of unknown functions. The degree of conservation of the mcr gene products among different species of methanogens varies. No correlation was found between the conservation of the G + C contents of the homologous genes and of the amino acid sequences of their products among the different bacteria. The comparison of RNA polymerase core subunit genes of Methanobacterium thermoautotrophicum as evolutionary markers with their equivalents in Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster showed that homologous polypeptide domains are encoded by different numbers of genes suggesting gene fusion of adjacent genes in the course of evolution. The archaebacterial subunits exhibit much stronger homology with their eukaryotic than with their eubacterial equivalents on the polypeptide sequence level. All the analyzed genes are preceded by ribosome binding sites of eubacterial type. In addition to known putative promoter sequences, conserved structural elements of the DNA were detected surrounding the transcription initiation sites of the mcr genes.Key words: archaebacteria, methanogens, gene structure, RNA polymerase, promoter.

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Gao, William, Thomas A. Jones, and Elena Rivas. "Discovery of 17 conserved structural RNAs in fungi." Nucleic Acids Research 49, no. 11 (June 4, 2021): 6128–43. http://dx.doi.org/10.1093/nar/gkab355.

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Abstract Many non-coding RNAs with known functions are structurally conserved: their intramolecular secondary and tertiary interactions are maintained across evolutionary time. Consequently, the presence of conserved structure in multiple sequence alignments can be used to identify candidate functional non-coding RNAs. Here, we present a bioinformatics method that couples iterative homology search with covariation analysis to assess whether a genomic region has evidence of conserved RNA structure. We used this method to examine all unannotated regions of five well-studied fungal genomes (Saccharomyces cerevisiae, Candida albicans, Neurospora crassa, Aspergillus fumigatus, and Schizosaccharomyces pombe). We identified 17 novel structurally conserved non-coding RNA candidates, which include four H/ACA box small nucleolar RNAs, four intergenic RNAs and nine RNA structures located within the introns and untranslated regions (UTRs) of mRNAs. For the two structures in the 3′ UTRs of the metabolic genes GLY1 and MET13, we performed experiments that provide evidence against them being eukaryotic riboswitches.

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31

RUHL, Donald D., Mary Ellen PUSATERI, and George L. ELICEIRI. "Multiple conserved segments of E1 small nucleolar RNA are involved in the formation of a ribonucleoprotein particle in frog oocytes." Biochemical Journal 348, no. 3 (June 7, 2000): 517–24. http://dx.doi.org/10.1042/bj3480517.

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E1/U17 small nucleolar RNA (snoRNA) is a box H/ACA snoRNA. To identify E1 RNA elements required for its assembly into a ribonucleoprotein (RNP) particle, we have made substitution mutations in evolutionarily conserved sequences and structures of frog E1 RNA. After E1 RNA was injected into the nucleus of frog oocytes, assembly of this exogenous RNA into an RNP was monitored by non-denaturing gel electrophoresis. Unexpectedly, nucleotide substitutions in many phylogenetically conserved segments of E1 RNA produced RNPs with abnormal gel-electrophoresis patterns. These RNA segments were at least nine conserved sequences and an apparently conserved structure. In another region needed for RNP formation, the requirement may be sequence(s) and/or structure. Base substitutions in each of these and in one additional conserved E1 RNA segment reduced the stability of this snoRNA in frog oocytes. Nucleolar localization was assayed by fluorescence microscopy after injection of fluorescein-labelled RNA. The H box (ANANNA) and the ACA box are both needed for efficient nucleolar localization of frog E1 RNA.

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Kedersha, N. L., M. C. Miquel, D. Bittner, and L. H. Rome. "Vaults. II. Ribonucleoprotein structures are highly conserved among higher and lower eukaryotes." Journal of Cell Biology 110, no. 4 (April 1, 1990): 895–901. http://dx.doi.org/10.1083/jcb.110.4.895.

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Vaults are cytoplasmic ribonucleoprotein structures that display a complex morphology reminiscent of the multiple arches which form cathedral vaults, hence their name. Previous studies on rat liver vaults (Kedersha, N. L., and L. H. Rome. 1986. J. Cell Biol. 103:699-709) have established that their composition is unlike that of any known class of RNA-containing particles in that they contain multiple copies of a unique small RNA and more than 50 copies of a single polypeptide of 104,000 Mr. We now report on the isolation of vaults from numerous species and show that vaults appear to be ubiquitous among eukaryotes, including mammals, amphibians (Rana catesbeiana and Xenopus laevis), avians (Gallus Gallus), and the lower eukaryote Dictyostelium discoideum. Electron microscopy reveals that vaults purified from these diverse species are similar both in their dimensions and morphology. The vaults from these various species are also similar in their polypeptide composition; each being composed of a major polypeptide with an approximate mass of 100 kD and several minor polypeptides with molecular masses similar to those seen in the rat. Antibodies raised against rat vaults recognize the major vault protein of all species including Dictyostelium. Vaults therefore appear to be strongly conserved and broadly distributed, suggesting that their function is essential to eukaryotic cells.

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Lee, Ji-Hye, Intekhab Alam, Kang Rok Han, Sunyoung Cho, Sungho Shin, Seokha Kang, Jai Myung Yang, and Kyung Hyun Kim. "Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase." Journal of General Virology 92, no. 7 (July 1, 2011): 1607–16. http://dx.doi.org/10.1099/vir.0.031104-0.

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Norovirus is one of the leading agents of gastroenteritis and is a major public health concern. In this study, the crystal structures of recombinant RNA-dependent RNA polymerase (RdRp) from murine norovirus-1 (MNV-1) and its complex with 5-fluorouracil (5FU) were determined at 2.5 Å resolution. Crystals with C2 symmetry revealed a dimer with half a dimer in the asymmetrical unit, and the protein exists predominantly as a monomer in solution, in equilibrium with a smaller population of dimers, trimers and hexamers. MNV-1 RdRp exhibited polymerization activity with a right-hand fold typical of polynucleotide polymerases. The metal ion modelled in close proximity to the active site was found to be coordinated tetrahedrally to the carboxyl groups of aspartate clusters. The orientation of 5FU observed in three molecules in the asymmetrical unit was found to be slightly different, but it was stabilized by a network of favourable interactions with the conserved active-site residues Arg185, Asp245, Asp346, Asp347 and Arg395. The information gained on the structural and functional features of MNV-1 RdRp will be helpful in understanding replication of norovirus and in designing novel therapeutic agents against this important pathogen.

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Nicolas Calderon, Kevin, Johan Fabian Galindo, and Clara Isabel Bermudez-Santana. "Evaluation of Conserved RNA Secondary Structures within and between Geographic Lineages of Zika Virus." Life 11, no. 4 (April 14, 2021): 344. http://dx.doi.org/10.3390/life11040344.

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Zika virus (ZIKV), without a vaccine or an effective treatment approved to date, has globally spread in the last century. The infection caused by ZIKV in humans has changed progressively from mild to subclinical in recent years, causing epidemics with greater infectivity, tropism towards new tissues and other related symptoms as a product of various emergent ZIKV–host cell interactions. However, it is still unknown why or how the RNA genome structure impacts those interactions in differential evolutionary origin strains. Moreover, the genomic comparison of ZIKV strains from the sequence-based phylogenetic analysis is well known, but differences from RNA structure comparisons have barely been studied. Thus, in order to understand the RNA genome variability of lineages of various geographic distributions better, 410 complete genomes in a phylogenomic scanning were used to study the conservation of structured RNAs. Our results show the contemporary landscape of conserved structured regions with unique conserved structured regions in clades or in lineages within circulating ZIKV strains. We propose these structures as candidates for further experimental validation to establish their potential role in vital functions of the viral cycle of ZIKV and their possible associations with the singularities of different outbreaks that lead to ZIKV populations to acquire nucleotide substitutions, which is evidence of the local structure genome differentiation.

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Sabarinathan, Radhakrishnan, Christian Anthon, Jan Gorodkin, and Stefan Seemann. "Multiple Sequence Alignments Enhance Boundary Definition of RNA Structures." Genes 9, no. 12 (December 4, 2018): 604. http://dx.doi.org/10.3390/genes9120604.

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Self-contained structured domains of RNA sequences have often distinct molecular functions. Determining the boundaries of structured domains of a non-coding RNA (ncRNA) is needed for many ncRNA gene finder programs that predict RNA secondary structures in aligned genomes because these methods do not necessarily provide precise information about the boundaries or the location of the RNA structure inside the predicted ncRNA. Even without having a structure prediction, it is of interest to search for structured domains, such as for finding common RNA motifs in RNA-protein binding assays. The precise definition of the boundaries are essential for downstream analyses such as RNA structure modelling, e.g., through covariance models, and RNA structure clustering for the search of common motifs. Such efforts have so far been focused on single sequences, thus here we present a comparison for boundary definition between single sequence and multiple sequence alignments. We also present a novel approach, named RNAbound, for finding the boundaries that are based on probabilities of evolutionarily conserved base pairings. We tested the performance of two different methods on a limited number of Rfam families using the annotated structured RNA regions in the human genome and their multiple sequence alignments created from 14 species. The results show that multiple sequence alignments improve the boundary prediction for branched structures compared to single sequences independent of the chosen method. The actual performance of the two methods differs on single hairpin structures and branched structures. For the RNA families with branched structures, including transfer RNA (tRNA) and small nucleolar RNAs (snoRNAs), RNAbound improves the boundary predictions using multiple sequence alignments to median differences of −6 and −11.5 nucleotides (nts) for left and right boundary, respectively (window size of 200 nts).

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Parsch, John, John M. Braverman, and Wolfgang Stephan. "Comparative Sequence Analysis and Patterns of Covariation in RNA Secondary Structures." Genetics 154, no. 2 (February 1, 2000): 909–21. http://dx.doi.org/10.1093/genetics/154.2.909.

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Abstract A novel method of RNA secondary structure prediction based on a comparison of nucleotide sequences is described. This method correctly predicts nearly all evolutionarily conserved secondary structures of five different RNAs: tRNA, 5S rRNA, bacterial ribonuclease P (RNase P) RNA, eukaryotic small subunit rRNA, and the 3′ untranslated region (UTR) of the Drosophila bicoid (bcd) mRNA. Furthermore, covariations occurring in the helices of these conserved RNA structures are analyzed. Two physical parameters are found to be important determinants of the evolution of compensatory mutations: the length of a helix and the distance between base-pairing nucleotides. For the helices of bcd 3′ UTR mRNA and RNase P RNA, a positive correlation between the rate of compensatory evolution and helix length is found. The analysis of Drosophila bcd 3′ UTR mRNA further revealed that the rate of compensatory evolution decreases with the physical distance between base-pairing residues. This result is in qualitative agreement with Kimura's model of compensatory fitness interactions, which assumes that mutations occurring in RNA helices are individually deleterious but become neutral in appropriate combinations.

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Michalak, Paula, Julita Piasecka, Barbara Szutkowska, Ryszard Kierzek, Ewa Biala, Walter N. Moss, and Elzbieta Kierzek. "Conserved Structural Motifs of Two Distant IAV Subtypes in Genomic Segment 5 RNA." Viruses 13, no. 3 (March 22, 2021): 525. http://dx.doi.org/10.3390/v13030525.

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The functionality of RNA is fully dependent on its structure. For the influenza A virus (IAV), there are confirmed structural motifs mediating processes which are important for the viral replication cycle, including genome assembly and viral packaging. Although the RNA of strains originating from distant IAV subtypes might fold differently, some structural motifs are conserved, and thus, are functionally important. Nowadays, NGS-based structure modeling is a source of new in vivo data helping to understand RNA biology. However, for accurate modeling of in vivo RNA structures, these high-throughput methods should be supported with other analyses facilitating data interpretation. In vitro RNA structural models complement such approaches and offer RNA structures based on experimental data obtained in a simplified environment, which are needed for proper optimization and analysis. Herein, we present the secondary structure of the influenza A virus segment 5 vRNA of A/California/04/2009 (H1N1) strain, based on experimental data from DMS chemical mapping and SHAPE using NMIA, supported by base-pairing probability calculations and bioinformatic analyses. A comparison of the available vRNA5 structures among distant IAV strains revealed that a number of motifs present in the A/California/04/2009 (H1N1) vRNA5 model are highly conserved despite sequence differences, located within previously identified packaging signals, and the formation of which in in virio conditions has been confirmed. These results support functional roles of the RNA secondary structure motifs, which may serve as candidates for universal RNA-targeting inhibitory methods.

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Liu, Yang, Jianbo Chen, Olga A. Nikolaitchik, Belete A. Desimmie, Steven Busan, Vinay K. Pathak, Kevin M. Weeks, and Wei-Shau Hu. "The roles of five conserved lentiviral RNA structures in HIV-1 replication." Virology 514 (January 2018): 1–8. http://dx.doi.org/10.1016/j.virol.2017.10.020.

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Werner, Arne. "Predicting translational diffusion of evolutionary conserved RNA structures by the nucleotide number." Nucleic Acids Research 39, no. 3 (November 10, 2010): e17-e17. http://dx.doi.org/10.1093/nar/gkq808.

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Pedersen, Jakob Skou, Gill Bejerano, Adam Siepel, Kate Rosenbloom, Kerstin Lindblad-Toh, Eric S. Lander, Jim Kent, Webb Miller, and David Haussler. "Identification and Classification of Conserved RNA Secondary Structures in the Human Genome." PLoS Computational Biology 2, no. 4 (April 21, 2006): e33. http://dx.doi.org/10.1371/journal.pcbi.0020033.

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Pedersen, Jakob Skou, Gill Bejerano, Adam Siepel, Kate R. Rosenbloom, Kerstin Lindblad-Toh, Eric S. Lander, Jim Kent, Webb Miller, and David Haussler. "Identification and Classification of Conserved RNA Secondary Structures in the Human Genome." PLoS Computational Biology preprint, no. 2006 (2005): e33. http://dx.doi.org/10.1371/journal.pcbi.0020033.eor.

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Yang, Y., V. C. Darbari, N. Zhang, D. Lu, R. Glyde, Y. P. Wang, J. T. Winkelman, et al. "Structures of the RNA polymerase- 54 reveal new and conserved regulatory strategies." Science 349, no. 6250 (August 20, 2015): 882–85. http://dx.doi.org/10.1126/science.aab1478.

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Xu, Zhenjiang, and David H. Mathews. "Multilign: an algorithm to predict secondary structures conserved in multiple RNA sequences." Bioinformatics 27, no. 5 (December 30, 2010): 626–32. http://dx.doi.org/10.1093/bioinformatics/btq726.

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Dunstan, Mark S., Debraj GuhaThakurta, David E. Draper, and Graeme L. Conn. "Coevolution of Protein and RNA Structures within a Highly Conserved Ribosomal Domain." Chemistry & Biology 12, no. 2 (February 2005): 201–6. http://dx.doi.org/10.1016/j.chembiol.2004.11.019.

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Sperschneider, Jana, Amitava Datta, and Michael J. Wise. "Predicting pseudoknotted structures across two RNA sequences." Bioinformatics 28, no. 23 (October 8, 2012): 3058–65. http://dx.doi.org/10.1093/bioinformatics/bts575.

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Abstract Motivation Laboratory RNA structure determination is demanding and costly and thus, computational structure prediction is an important task. Single sequence methods for RNA secondary structure prediction are limited by the accuracy of the underlying folding model, if a structure is supported by a family of evolutionarily related sequences, one can be more confident that the prediction is accurate. RNA pseudoknots are functional elements, which have highly conserved structures. However, few comparative structure prediction methods can handle pseudoknots due to the computational complexity. Results A comparative pseudoknot prediction method called DotKnot-PW is introduced based on structural comparison of secondary structure elements and H-type pseudoknot candidates. DotKnot-PW outperforms other methods from the literature on a hand-curated test set of RNA structures with experimental support. Availability DotKnot-PW and the RNA structure test set are available at the web site http://dotknot.csse.uwa.edu.au/pw. Contact janaspe@csse.uwa.edu.au Supplementary information Supplementary data are available at Bioinformatics online.

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Thiel, Bernhard, Roman Ochsenreiter, Veerendra Gadekar, Andrea Tanzer, and Ivo L. Hofacker. "RNA Structure Elements Conserved between Mouse and 59 Other Vertebrates." Genes 9, no. 8 (August 1, 2018): 392. http://dx.doi.org/10.3390/genes9080392.

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In this work, we present a computational screen conducted for functional RNA structures, resulting in over 100,000 conserved RNA structure elements found in alignments of mouse (mm10) against 59 other vertebrates. We explicitly included masked repeat regions to explore the potential of transposable elements and low-complexity regions to give rise to regulatory RNA elements. In our analysis pipeline, we implemented a four-step procedure: (i) we screened genome-wide alignments for potential structure elements using RNAz-2, (ii) realigned and refined candidate loci with LocARNA-P, (iii) scored candidates again with RNAz-2 in structure alignment mode, and (iv) searched for additional homologous loci in mouse genome that were not covered by genome alignments. The 3’-untranslated regions (3’-UTRs) of protein-coding genes and small noncoding RNAs are enriched for structures, while coding sequences are depleted. Repeat-associated loci make up about 95% of the homologous loci identified and are, as expected, predominantly found in intronic and intergenic regions. Nevertheless, we report the structure elements enriched in specific genome elements, such as 3’-UTRs and long noncoding RNAs (lncRNAs). We provide full access to our results via a custom UCSC genome browser trackhub freely available on our website (http://rna.tbi.univie.ac.at/trackhubs/#RNAz).

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Rivas, Elena. "RNA structure prediction using positive and negative evolutionary information." PLOS Computational Biology 16, no. 10 (October 30, 2020): e1008387. http://dx.doi.org/10.1371/journal.pcbi.1008387.

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Knowing the structure of conserved structural RNAs is important to elucidate their function and mechanism of action. However, predicting a conserved RNA structure remains unreliable, even when using a combination of thermodynamic stability and evolutionary covariation information. Here we present a method to predict a conserved RNA structure that combines the following three features. First, it uses significant covariation due to RNA structure and removes spurious covariation due to phylogeny. Second, it uses negative evolutionary information: basepairs that have variation but no significant covariation are prevented from occurring. Lastly, it uses a battery of probabilistic folding algorithms that incorporate all positive covariation into one structure. The method, named CaCoFold (Cascade variation/covariation Constrained Folding algorithm), predicts a nested structure guided by a maximal subset of positive basepairs, and recursively incorporates all remaining positive basepairs into alternative helices. The alternative helices can be compatible with the nested structure such as pseudoknots, or overlapping such as competing structures, base triplets, or other 3D non-antiparallel interactions. We present evidence that CaCoFold predictions are consistent with structures modeled from crystallography.

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Alhatlani, Bader Y. "In silico identification of conserved cis-acting RNA elements in the SARS-CoV-2 genome." Future Virology 15, no. 7 (July 2020): 409–17. http://dx.doi.org/10.2217/fvl-2020-0163.

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Aim: The aim of this study was to computationally predict conserved RNA sequences and structures known as cis-acting RNA elements (CREs) in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome. Materials & methods: Bioinformatics tools were used to analyze and predict CREs by obtaining viral sequences from available databases. Results: Computational analysis revealed the presence of RNA stem-loop structures within the 3′ end of the ORF1ab region analogous to previously identified SARS-CoV genomic packaging signals. Alignment-based RNA secondary structure predictions of the 5′ end of the SARS-CoV-2 genome also identified conserved CREs. Conclusion: These CREs may be potential vaccine and/or antiviral therapeutic targets; however, further studies are warranted to confirm their roles in the SARS-CoV-2 life cycle.

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Cheng, Ju-Chien, Ming-Fu Chang, and Shin C. Chang. "Specific Interaction between the Hepatitis C Virus NS5B RNA Polymerase and the 3′ End of the Viral RNA." Journal of Virology 73, no. 8 (August 1, 1999): 7044–49. http://dx.doi.org/10.1128/jvi.73.8.7044-7049.1999.

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ABSTRACT Hepatitis C virus (HCV) NS5B protein is the viral RNA-dependent RNA polymerase capable of directing RNA synthesis. In this study, an electrophoretic mobility shift assay demonstrated the interaction between a partially purified recombinant NS5B protein and a 3′ viral genomic RNA with or without the conserved 98-nucleotide tail. The NS5B-RNA complexes were specifically competed away by the unlabeled homologous RNA but not by the viral 5′ noncoding region and very poorly by the 3′ conserved 98-nucleotide tail. A 3′ coding region with conserved stem-loop structures rather than the 3′ noncoding region of the HCV genome is critical for the specific binding of NS5B. Nevertheless, no direct interaction between the 3′ coding region and the HCV NS5A protein was detected. Furthermore, two independent RNA-binding domains (RBDs) of NS5B were identified, RBD1, from amino acid residues 83 to 194, and RBD2, from residues 196 to 298. Interestingly, the conserved motifs of RNA-dependent RNA polymerase for putative RNA binding (220-DxxxxD-225) and template/primer position (282-S/TGxxxTxxxNS/T-292) are present in the RBD2. Nevertheless, the RNA-binding activity of RBD2 was abolished when it was linked to the carboxy-terminal half of the NS5B. These results provide some clues to understanding the initiation of HCV replication.

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Kiss, T., M. L. Bortolin, and W. Filipowicz. "Characterization of the intron-encoded U19 RNA, a new mammalian small nucleolar RNA that is not associated with fibrillarin." Molecular and Cellular Biology 16, no. 4 (April 1996): 1391–400. http://dx.doi.org/10.1128/mcb.16.4.1391.

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We have characterized a new member (U19) of a group of mammalian small nuclear RNAs that are not precipitable with antibodies against fibrillarin, a conserved nucleolar protein associated with most of the small nucleolar RNAs characterized to date. Human U19 RNA is 200 nucleotides long and possesses 5'-monophosphate and 3'-hydroxyl termini. It lacks functional boxes C and D, sequence motifs required for fibrillarin binding in many other snoRNAs. Human and mouse RNA are 86% homologous and can be folded into similar secondary structures, a finding supported by the results of nuclease probing of the RNA. In the human genome, U19 RNA is encoded in the intron of an as yet not fully characterized gene and could be faithfully processed from a longer precursor RNA in HeLa cell extracts. During fractionation of HeLa cell nucleolar extracts on glycerol gradients, U19 RNA was associated with higher-order structures of approximately 65S, cosedimenting with complexes containing 7-2/MRP RNA, a conserved nucleolar RNA shown to be involved in 5.8S rRNA processing in yeast cells.

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Journal articles on the topic 'Conserved RNA Structures'

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