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1

Markus, Damien, Aurore Pelletier, Muriel Boube, et al. "The pleiotropic functions of Pri smORF peptides synchronize leg development regulators." PLOS Genetics 19, no. 10 (2023): e1011004. http://dx.doi.org/10.1371/journal.pgen.1011004.

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The last decade witnesses the emergence of the abundant family of smORF peptides, encoded by small ORF (<100 codons), whose biological functions remain largely unexplored. Bioinformatic analyses here identify hundreds of putative smORF peptides expressed in Drosophila imaginal leg discs. Thanks to a functional screen in leg, we found smORF peptides involved in morphogenesis, including the pioneer smORF peptides Pri. Since we identified its target Ubr3 in the epidermis and pri was known to control leg development through poorly understood mechanisms, we investigated the role of Ubr3 in media
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2

Lyapina, Irina, Vadim Ivanov, and Igor Fesenko. "Peptidome: Chaos or Inevitability." International Journal of Molecular Sciences 22, no. 23 (2021): 13128. http://dx.doi.org/10.3390/ijms222313128.

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Thousands of naturally occurring peptides differing in their origin, abundance and possible functions have been identified in the tissue and biological fluids of vertebrates, insects, fungi, plants and bacteria. These peptide pools are referred to as intracellular or extracellular peptidomes, and besides a small proportion of well-characterized peptide hormones and defense peptides, are poorly characterized. However, a growing body of evidence suggests that unknown bioactive peptides are hidden in the peptidomes of different organisms. In this review, we present a comprehensive overview of the
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3

Douka, Katerina, Isabel Birds, Dapeng Wang, et al. "Cytoplasmic long noncoding RNAs are differentially regulated and translated during human neuronal differentiation." RNA 27, no. 9 (2021): 1082–101. http://dx.doi.org/10.1261/rna.078782.121.

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The expression of long noncoding RNAs is highly enriched in the human nervous system. However, the function of neuronal lncRNAs in the cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncRNAs with the translation machinery and the functional consequences during neuronal differentiation of human SH-SY5Y cells. We discovered 237 cytoplasmic lncRNAs up-regulated during early neuronal differentiation, 58%–70% of which are associated with polysome translation complexes. Among these polysome-associated lncRNAs, we f
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Bonilauri, Bernardo, Fabiola Barbieri Holetz, and Bruno Dallagiovanna. "Long Non-Coding RNAs Associated with Ribosomes in Human Adipose-Derived Stem Cells: From RNAs to Microproteins." Biomolecules 11, no. 11 (2021): 1673. http://dx.doi.org/10.3390/biom11111673.

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Ribosome profiling reveals the translational dynamics of mRNAs by capturing a ribosomal footprint snapshot. Growing evidence shows that several long non-coding RNAs (lncRNAs) contain small open reading frames (smORFs) that are translated into functional peptides. The difficulty in identifying bona-fide translated smORFs is a constant challenge in experimental and bioinformatics fields due to their unconventional characteristics. This motivated us to isolate human adipose-derived stem cells (hASC) from adipose tissue and perform a ribosome profiling followed by bioinformatics analysis of transc
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5

Dozier, Christine, Audrey Montigny, Mireia Viladrich, et al. "Small ORFs as New Regulators of Pri-miRNAs and miRNAs Expression in Human and Drosophila." International Journal of Molecular Sciences 23, no. 10 (2022): 5764. http://dx.doi.org/10.3390/ijms23105764.

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MicroRNAs (miRNAs) are small regulatory non-coding RNAs, resulting from the cleavage of long primary transcripts (pri-miRNAs) in the nucleus by the Microprocessor complex generating precursors (pre-miRNAs) that are then exported to the cytoplasm and processed into mature miRNAs. Some miRNAs are hosted in pri-miRNAs annotated as long non-coding RNAs (lncRNAs) and defined as MIRHGs (for miRNA Host Genes). However, several lnc pri-miRNAs contain translatable small open reading frames (smORFs). If smORFs present within lncRNAs can encode functional small peptides, they can also constitute cis-regu
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6

Southan, Christopher. "Last rolls of the yoyo: Assessing the human canonical protein count." F1000Research 6 (April 7, 2017): 448. http://dx.doi.org/10.12688/f1000research.11119.1.

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In 2004, when the protein estimate from the finished human genome was only 24,000, the surprise was compounded as reviewed estimates fell to 19,000 by 2014. However, variability in the total canonical protein counts (i.e. excluding alternative splice forms) of open reading frames (ORFs) in different annotation portals persists. This work assesses these differences and possible causes. A 16-year analysis of Ensembl and UniProtKB/Swiss-Prot shows convergence to a protein number of ~20,000. The former had shown some yo-yoing, but both have now plateaued. Nine major annotation portals, reviewed at
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7

Wan, Linrong, Wenfu Xiao, Ziyan Huang, et al. "Systematic identification of smORFs in domestic silkworm (Bombyx mori)." PeerJ 11 (January 13, 2023): e14682. http://dx.doi.org/10.7717/peerj.14682.

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The silkworm (Bombyx mori) is not only an excellent model species, but also an important agricultural economic insect. Taking it as the research object, its advantages of low maintenance cost and no biohazard risks are considered. Small open reading frames (smORFs) are an important class of genomic elements that can produce bioactive peptides. However, the smORFs in silkworm had been poorly identified and studied. To further study the smORFs in silkworm, systematic genome-wide identification is essential. Here, we identified and analyzed smORFs in the silkworm using comprehensive methods. Our
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8

Cao, Yipeng, Rui Yang, Imshik Lee, et al. "Prediction of LncRNA-encoded small peptides in glioma and oligomer channel functional analysis using in silico approaches." PLOS ONE 16, no. 3 (2021): e0248634. http://dx.doi.org/10.1371/journal.pone.0248634.

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Glioma is a lethal malignant brain cancer, and many reports have shown that abnormalities in the behavior of water and ion channels play an important role in regulating tumor proliferation, migration, apoptosis, and differentiation. Recently, new studies have suggested that some long noncoding RNAs containing small open reading frames can encode small peptides and form oligomers for water or ion regulation. However, because the peptides are difficult to identify, their functional mechanisms are far from being clearly understood. In this study, we used bioinformatics methods to identify and eva
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9

Magny, Emile G., Jose Ignacio Pueyo, Frances M. G. Pearl, et al. "Conserved Regulation of Cardiac Calcium Uptake by Peptides Encoded in Small Open Reading Frames." Science 341, no. 6150 (2013): 1116–20. http://dx.doi.org/10.1126/science.1238802.

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Small open reading frames (smORFs) are short DNA sequences that are able to encode small peptides of less than 100 amino acids. Study of these elements has been neglected despite thousands existing in our genomes. We and others previously showed that peptides as short as 11 amino acids are translated and provide essential functions during insect development. Here, we describe two peptides of less than 30 amino acids regulating calcium transport, and hence influencing regular muscle contraction, in the Drosophila heart. These peptides seem conserved for more than 550 million years in a range of
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10

Dragomir, Mihnea P., Ganiraju C. Manyam, Leonie Florence Ott, et al. "FuncPEP: A Database of Functional Peptides Encoded by Non-Coding RNAs." Non-Coding RNA 6, no. 4 (2020): 41. http://dx.doi.org/10.3390/ncrna6040041.

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Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less than 100 amino acids. The sequences encoding these peptides are known as small open reading frames (smORFs), many initiating with the traditional AUG start codon but terminating with atypical stop codons, suggesting a different biogenesis. The ncRNA-encoded peptides (ncPEPs) are gradually b
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11

Immarigeon, Clément, Yohan Frei, Sofie Y. N. Delbare, et al. "Identification of a micropeptide and multiple secondary cell genes that modulateDrosophilamale reproductive success." Proceedings of the National Academy of Sciences 118, no. 15 (2021): e2001897118. http://dx.doi.org/10.1073/pnas.2001897118.

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Even in well-characterized genomes, many transcripts are considered noncoding RNAs (ncRNAs) simply due to the absence of large open reading frames (ORFs). However, it is now becoming clear that many small ORFs (smORFs) produce peptides with important biological functions. In the process of characterizing the ribosome-bound transcriptome of an important cell type of the seminal fluid-producing accessory gland ofDrosophila melanogaster, we detected an RNA, previously thought to be noncoding, calledmale-specific abdominal(msa). Notably,msais nested in the HOX gene cluster of the Bithorax complex
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12

Pueyo, Jose I., Jorge Salazar, Carolina Grincho, Jimena Berni, Benjamin P. Towler, and Sarah F. Newbury. "Purriato is a conserved small open reading frame gene that interacts with the CASA pathway to regulate muscle homeostasis and epithelial tissue growth in Drosophila." Frontiers in Cell and Developmental Biology 11 (March 10, 2023). http://dx.doi.org/10.3389/fcell.2023.1117454.

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Recent advances in proteogenomic techniques and bioinformatic pipelines have permitted the detection of thousands of translated small Open Reading Frames (smORFs), which contain less than 100 codons, in eukaryotic genomes. Hundreds of these actively translated smORFs display conserved sequence, structure and evolutionary signatures indicating that the translated peptides could fulfil important biological roles. Despite their abundance, only tens of smORF genes have been fully characterised; these act mainly as regulators of canonical proteins involved in essential cellular processes. Important
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13

Bosch, Justin A., Berrak Ugur, Israel Pichardo-Casas, et al. "Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila." eLife 11 (November 8, 2022). http://dx.doi.org/10.7554/elife.82709.

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Naturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open reading frames (smORFs). Here, we describe two peptides in Drosophila encoded by conserved smORFs, Sloth1 and Sloth2. These peptides are translated from the same bicistronic transcript and share sequence similarities, suggesting that they encode paralogs. Yet, Sloth1 and Sloth2 are not functionally redundant, and loss of either peptide causes animal lethality, redu
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14

Aspden, Julie L., Ying Chen Eyre-Walker, Rose J. Phillips, et al. "Extensive translation of small Open Reading Frames revealed by Poly-Ribo-Seq." eLife 3 (August 21, 2014). http://dx.doi.org/10.7554/elife.03528.

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Thousands of small Open Reading Frames (smORFs) with the potential to encode small peptides of fewer than 100 amino acids exist in our genomes. However, the number of smORFs actually translated, and their molecular and functional roles are still unclear. In this study, we present a genome-wide assessment of smORF translation by ribosomal profiling of polysomal fractions in Drosophila. We detect two types of smORFs bound by multiple ribosomes and thus undergoing productive translation. The ‘longer’ smORFs of around 80 amino acids resemble canonical proteins in translational metrics and conserva
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15

Ventroux, Magali, and Marie-Francoise Noirot-Gros. "Prophage-encoded small protein YqaH counteracts the activities of the replication initiator DnaA in Bacillus subtilis." Microbiology 168, no. 11 (2022). http://dx.doi.org/10.1099/mic.0.001268.

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Bacterial genomes harbour cryptic prophages that are mostly transcriptionally silent with many unannotated genes. Still, cryptic prophages may contribute to their host fitness and phenotypes. In Bacillus subtilis, the yqaF-yqaN operon belongs to the prophage element skin, and is tightly repressed by the Xre-like repressor SknR. This operon contains several small ORFs (smORFs) potentially encoding small-sized proteins. The smORF-encoded peptide YqaH was previously reported to bind to the replication initiator DnaA. Here, using a yeast two-hybrid assay, we found that YqaH binds to the DNA bindin
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16

Peng, Zhao, Jiaqiang Li, Xingpeng Jiang, and Cuihong Wan. "sOCP: a framework predicting smORF coding potential based on TIS and in-frame features and effectively applied in the human genome." Briefings in Bioinformatics 25, no. 3 (2024). http://dx.doi.org/10.1093/bib/bbae147.

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Abstract Small open reading frames (smORFs) have been acknowledged to play various roles on essential biological pathways and affect human beings from diabetes to tumorigenesis. Predicting smORFs in silico is quite a prerequisite for processing the omics data. Here, we proposed the smORF-coding-potential-predicting framework, sOCP, which provides functions to construct a model for predicting novel smORFs in some species. The sOCP model constructed in human was based on in-frame features and the nucleotide bias around the start codon, and the small feature subset was proved to be competent enou
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17

Fan, Si-Min, Ze-Qi Li, Shi-Zhe Zhang, et al. "Multi-integrated approach for unraveling small open reading frames potentially associated with secondary metabolism in Streptomyces." mSystems, September 15, 2023. http://dx.doi.org/10.1128/msystems.00245-23.

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ABSTRACT Small open reading frames (smORFs) are widely distributed in various living organisms. However, their functions remain largely unexplored. In addition, annotation and detection of smORFs are limited using existing methods and hindered by their specific properties. In this study, we systematically investigated smORFs and smORF-encoded peptides (SEPs) in Streptomyces , which are well-known bacterial producers of diverse bioactive secondary metabolites. We established a peptidogenomic workflow based on multi-integrated comprehensive database search and database-independent de novo sequen
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18

Guerra-Almeida, Diego, Diogo Antonio Tschoeke, and Rodrigo Nunes-da-Fonseca. "Understanding small ORF diversity through a comprehensive transcription feature classification." DNA Research 28, no. 5 (2021). http://dx.doi.org/10.1093/dnares/dsab007.

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Abstract Small open reading frames (small ORFs/sORFs/smORFs) are potentially coding sequences smaller than 100 codons that have historically been considered junk DNA by gene prediction software and in annotation screening; however, the advent of next-generation sequencing has contributed to the deeper investigation of junk DNA regions and their transcription products, resulting in the emergence of smORFs as a new focus of interest in systems biology. Several smORF peptides were recently reported in non-canonical mRNAs as new players in numerous biological contexts; however, their relevance is
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19

Jain, Niyati, Felix Richter, Ivan Adzhubei, Andrew J. Sharp, and Bruce D. Gelb. "Small open reading frames: a comparative genetics approach to validation." BMC Genomics 24, no. 1 (2023). http://dx.doi.org/10.1186/s12864-023-09311-7.

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AbstractOpen reading frames (ORFs) with fewer than 100 codons are generally not annotated in genomes, although bona fide genes of that size are known. Newer biochemical studies have suggested that thousands of small protein-coding ORFs (smORFs) may exist in the human genome, but the true number and the biological significance of the micropeptides they encode remain uncertain. Here, we used a comparative genomics approach to identify high-confidence smORFs that are likely protein-coding. We identified 3,326 high-confidence smORFs using constraint within human populations and evolutionary conser
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20

Fesenko, Igor, Svetlana A. Shabalina, Anna Mamaeva, et al. "A vast pool of lineage-specific microproteins encoded by long non-coding RNAs in plants." Nucleic Acids Research, September 27, 2021. http://dx.doi.org/10.1093/nar/gkab816.

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Abstract Pervasive transcription of eukaryotic genomes results in expression of long non-coding RNAs (lncRNAs) most of which are poorly conserved in evolution and appear to be non-functional. However, some lncRNAs have been shown to perform specific functions, in particular, transcription regulation. Thousands of small open reading frames (smORFs, <100 codons) located on lncRNAs potentially might be translated into peptides or microproteins. We report a comprehensive analysis of the conservation and evolutionary trajectories of lncRNAs-smORFs from the moss Physcomitrium patens across tr
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21

Sruthi, K. Bharathan, Athira Menon, Akash P, and Eppurath Vasudevan Soniya. "Pervasive translation of small open reading frames in plant long non-coding RNAs." Frontiers in Plant Science 13 (October 24, 2022). http://dx.doi.org/10.3389/fpls.2022.975938.

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Long non-coding RNAs (lncRNAs) are primarily recognized as non-coding transcripts longer than 200 nucleotides with low coding potential and are present in both eukaryotes and prokaryotes. Recent findings reveal that lncRNAs can code for micropeptides in various species. Micropeptides are generated from small open reading frames (smORFs) and have been discovered frequently in short mRNAs and non-coding RNAs, such as lncRNAs, circular RNAs, and pri-miRNAs. The most accepted definition of a smORF is an ORF containing fewer than 100 codons, and ribosome profiling and mass spectrometry are the most
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22

Hara, Tomoaki, Sikun Meng, Yoshiko Tsuji, et al. "RN7SL1 may be translated under oncogenic conditions." Proceedings of the National Academy of Sciences 121, no. 12 (2024). http://dx.doi.org/10.1073/pnas.2312322121.

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RN7SL1 (RNA component of signal recognition particle 7SL1), a component of the signal recognition particle, is a non-coding RNA possessing a small ORF (smORF). However, whether it is translated into peptides is unknown. Here, we generated the RN7SL1-Green Fluorescent Protein (GFP) gene, in which the smORF of RN7SL1 was replaced by GFP, introduced it into 293T cells, and observed cells emitting GFP fluorescence. Furthermore, RNA-seq of GFP-positive cells revealed that they were in an oncogenic state, suggesting that RN7SL1 smORF may be translated under special conditions.
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23

Dib, Azza, Jennifer Zanet, Alexandra Mancheno-Ferris, et al. "Pri smORF Peptides Are Wide Mediators of Ecdysone Signaling, Contributing to Shape Spatiotemporal Responses." Frontiers in Genetics 12 (August 30, 2021). http://dx.doi.org/10.3389/fgene.2021.714152.

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There is growing evidence that peptides encoded by small open-reading frames (sORF or smORF) can fulfill various cellular functions and define a novel class regulatory molecules. To which extend transcripts encoding only smORF peptides compare with canonical protein-coding genes, yet remain poorly understood. In particular, little is known on whether and how smORF-encoding RNAs might need tightly regulated expression within a given tissue, at a given time during development. We addressed these questions through the analysis of Drosophila polished rice (pri, a.k.a. tarsal less or mille pattes),
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24

Hu, Fengyuan, Jia Lu, Louise S. Matheson, Manuel D. Díaz-Muñoz, Alexander Saveliev, and Martin Turner. "ORFLine: a bioinformatic pipeline to prioritize small open reading frames identifies candidate secreted small proteins from lymphocytes." Bioinformatics, May 10, 2021. http://dx.doi.org/10.1093/bioinformatics/btab339.

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Abstract Motivation The annotation of small open reading frames (smORFs) of <100 codons (<300 nucleotides) is challenging due to the large number of such sequences in the genome. Results In this study, we developed a computational pipeline, which we have named ORFLine, that stringently identifies smORFs and classifies them according to their position within transcripts. We identified a total of 5744 unique smORFs in datasets from mouse B and T lymphocytes and systematically characterized them using ORFLine. We further searched smORFs for the presence of a signal peptide, which pr
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25

Magny, Emile G., Ana Isabel Platero, Sarah A. Bishop, Jose I. Pueyo, Daniel Aguilar-Hidalgo, and Juan Pablo Couso. "Pegasus, a small extracellular peptide enhancing short-range diffusion of Wingless." Nature Communications 12, no. 1 (2021). http://dx.doi.org/10.1038/s41467-021-25785-z.

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AbstractSmall Open Reading Frames (smORFs) coding for peptides of less than 100 amino-acids are an enigmatic and pervasive gene class, found in the tens of thousands in metazoan genomes. Here we reveal a short 80 amino-acid peptide (Pegasus) which enhances Wingless/Wnt1 protein short-range diffusion and signalling. During Drosophila wing development, Wingless has sequential functions, including late induction of proneural gene expression and wing margin development. Pegasus mutants produce wing margin defects and proneural expression loss similar to those of Wingless. Pegasus is secreted, and
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26

Coelho, Luis Pedro, Célio Dias Santos‐Júnior, and Cesar de la Fuente‐Nunez. "Challenges in computational discovery of bioactive peptides in ’omics data." PROTEOMICS, March 8, 2024. http://dx.doi.org/10.1002/pmic.202300105.

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AbstractPeptides have a plethora of activities in biological systems that can potentially be exploited biotechnologically. Several peptides are used clinically, as well as in industry and agriculture. The increase in available ’omics data has recently provided a large opportunity for mining novel enzymes, biosynthetic gene clusters, and molecules. While these data primarily consist of DNA sequences, other types of data provide important complementary information. Due to their size, the approaches proven successful at discovering novel proteins of canonical size cannot be naïvely applied to the
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27

Gallois, Maylis, Delphine Menoret, Simon Marques-Prieto, et al. "Pri peptides temporally coordinate transcriptional programs during epidermal differentiation." Science Advances 10, no. 6 (2024). http://dx.doi.org/10.1126/sciadv.adg8816.

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To achieve a highly differentiated state, cells undergo multiple transcriptional processes whose coordination and timing are not well understood. In Drosophila embryonic epidermal cells, polished-rice (Pri) smORF peptides act as temporal mediators of ecdysone to activate a transcriptional program leading to cell shape remodeling. Here, we show that the ecdysone/Pri axis concomitantly represses the transcription of a large subset of cuticle genes to ensure proper differentiation of the insect exoskeleton. The repression relies on the transcription factor Ken and persists for several days throug
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28

Li, Hui, Li Xiao, Lili Zhang, et al. "FSPP: A Tool for Genome-Wide Prediction of smORF-Encoded Peptides and Their Functions." Frontiers in Genetics 9 (April 5, 2018). http://dx.doi.org/10.3389/fgene.2018.00096.

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29

Moysidis, Dimitrios V., Stylianos Daios, Vasileios Anastasiou, et al. "Association of clinical, laboratory and imaging biomarkers with the occurrence of acute myocardial infarction in patients without standard modifiable risk factors – rationale and design of the “Beyond-SMuRFs Study”." BMC Cardiovascular Disorders 23, no. 1 (2023). http://dx.doi.org/10.1186/s12872-023-03180-4.

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Abstract Background Acute myocardial infarction (AMI) remains the leading cause of mortality worldwide. The majority of patients who suffer an AMI have a history of at least one of the standard modifiable risk factors (SMuRFs): smoking, hypertension, dyslipidemia, and diabetes mellitus. However, emerging scientific evidence recognizes a clinically significant and increasing proportion of patients presenting with AMI without any SMuRF (SMuRF-less patients). To date, there are no adequate data to define specific risk factors or biomarkers associated with the development of AMIs in these patients
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30

Ray, Suparna, Miriam I. Rosenberg, Hélène Chanut-Delalande, et al. "The mlpt/Ubr3/Svb module comprises an ancient developmental switch for embryonic patterning." eLife 8 (March 21, 2019). http://dx.doi.org/10.7554/elife.39748.

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Small open reading frames (smORFs) encoding ‘micropeptides’ exhibit remarkable evolutionary complexity. Conserved peptides encoded by mille-pattes (mlpt)/polished rice (pri)/tarsal less (tal) are essential for embryo segmentation in Tribolium but, in Drosophila, function in terminal epidermal differentiation and patterning of adult legs. Here, we show that a molecular complex identified in Drosophila epidermal differentiation, comprising Mlpt peptides, ubiquitin-ligase Ubr3 and transcription factor Shavenbaby (Svb), represents an ancient developmental module required for early insect embryo pa
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Turchetti, Benedetta, Pietro Buzzini, and Marcelo Baeza. "A genomic approach to analyze the cold adaptation of yeasts isolated from Italian Alps." Frontiers in Microbiology 13 (November 8, 2022). http://dx.doi.org/10.3389/fmicb.2022.1026102.

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Microorganisms including yeasts are responsible for mineralization of organic matter in cold regions, and their characterization is critical to elucidate the ecology of such environments on Earth. Strategies developed by yeasts to survive in cold environments have been increasingly studied in the last years and applied to different biotechnological applications, but their knowledge is still limited. Microbial adaptations to cold include the synthesis of cryoprotective compounds, as well as the presence of a high number of genes encoding the synthesis of proteins/enzymes characterized by a redu
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