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Journal articles on the topic 'Nucleic acid'

Author: Grafiati

Published: 4 June 2021

Last updated: 8 June 2024

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1

Yildirim, Asil, Brad Varner, Monika Sharma, Liang Fang, and Michael Feig. "2P120 Conformational Sampling of Nucleic Acids in Cellular Environments(05A. Nucleic acid: Structure & Property,Poster)." Seibutsu Butsuri 53, supplement1-2 (2013): S178. http://dx.doi.org/10.2142/biophys.53.s178_6.

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2

Bergen, Jamie M., and Suzie H. Pun. "Peptide-Enhanced Nucleic Acid Delivery." MRS Bulletin 30, no. 9 (September 2005): 663–67. http://dx.doi.org/10.1557/mrs2005.194.

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AbstractNumerous barriers, both extracellular and intracellular, hinder successful and efficient nonviral nucleic acid delivery. Due to their small size and ability to specifically recognize and interact with molecular targets, peptides can be incorporated as modular elements into synthetic nucleic acid delivery systems to overcome many of these barriers. Three classes of peptides that have frequently been integrated as components in nucleic acid delivery systems include cell-penetrating peptides (CPPs), endosomal release peptides, and nuclear localization sequences (NLSs).Various additional classes of peptides show promise for enhancing nucleic acid delivery by targeting cell surface receptors, inhibiting nuclease activity, and directing nucleic acids toward intracellular targets. In addition to a review of the various existing approaches to peptide-enhanced nucleic acid delivery, this article will discuss strategies for the development of new peptides and approaches for the incorporation of these peptides into nucleic acid delivery systems.

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3

Stoddard, Barry L., Anastasia Khvorova, David R. Corey, William S. Dynan, and Keith R. Fox. "Editorial: Nucleic Acids Research and Nucleic Acid Therapeutics." Nucleic Acids Research 46, no. 4 (February 23, 2018): 1563–64. http://dx.doi.org/10.1093/nar/gky059.

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4

Reece, Richard. "The messenger: the structure of RNA." Biochemist 28, no. 2 (April 1, 2006): 33–35. http://dx.doi.org/10.1042/bio02802033.

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In the early part of the 20th Century, the nature of nucleic acid and what its role was within the cell were a bit of a mystery. DNA itself was first isolated as far back as 1869 by the Swiss chemist Johann Friedrich Miescher. He separated nuclei from the cytoplasm of cells and then isolated an acidic substance from these nuclei that he called nuclein1. Chemical tests by Miescher showed that nuclein contained large amounts of phosphorus and no sulphur, characteristics that differentiated it from proteins1. The first step in determining the structure of nucleic acid (either DNA or RNA) would be to identify its precise composition. RNA was considered a more approachable target for composition analysis because the simple treatment of RNA with hydroxide rapidly and completely hydrolyses the molecule to its individual component nucleotides. DNA, on the other hand, is resistant to such treatment.

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5

Zhou, Ding, Guy Schepers, and Arthur Van Aerschot. "A Simple Nucleic Acid Alternative: Aminopropyl Nucleic Acids (APNAs)." Nucleosides, Nucleotides and Nucleic Acids 26, no. 10-12 (November 26, 2007): 1665–68. http://dx.doi.org/10.1080/15257770701493625.

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6

Berman, Helen M., John Westbrook, Zukang Feng, Lisa Iype, Bohdan Schneider, and Christine Zardecki. "The Nucleic Acid Database." Acta Crystallographica Section D Biological Crystallography 58, no. 6 (May 29, 2002): 889–98. http://dx.doi.org/10.1107/s0907444902003487.

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The Nucleic Acid Database was established in 1991 as a resource to assemble and distribute structural information about nucleic acids. Over the years, the NDB has developed generalized software for processing, archiving, querying and distributing structural data for nucleic acid-containing structures. The architecture and capabilities of the Nucleic Acid Database, as well as some of the research enabled by this resource, are presented in this article.

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7

Heras, Sara R., M. Carmen Thomas, Francisco Macias, Manuel E. Patarroyo, Carlos Alonso, and Manuel C. López. "Nucleic-acid-binding properties of the C2-L1Tc nucleic acid chaperone encoded by L1Tc retrotransposon." Biochemical Journal 424, no. 3 (December 10, 2009): 479–90. http://dx.doi.org/10.1042/bj20090766.

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It has been reported previously that the C2-L1Tc protein located in the Trypanosoma cruzi LINE (long interspersed nuclear element) L1Tc 3′ terminal end has NAC (nucleic acid chaperone) activity, an essential activity for retrotransposition of LINE-1. The C2-L1Tc protein contains two cysteine motifs of a C2H2 type, similar to those present in TFIIIA (transcription factor IIIA). The cysteine motifs are flanked by positively charged amino acid regions. The results of the present study show that the C2-L1Tc recombinant protein has at least a 16-fold higher affinity for single-stranded than for double-stranded nucleic acids, and that it exhibits a clear preference for RNA binding over DNA. The C2-L1Tc binding profile (to RNA and DNA) corresponds to a non-co-operative-binding model. The zinc fingers present in C2-L1Tc have a different binding affinity to nucleic acid molecules and also different NAC activity. The RRR and RRRKEK [NLS (nuclear localization sequence)] sequences, as well as the C2H2 zinc finger located immediately downstream of these basic stretches are the main motifs responsible for the strong affinity of C2-L1Tc to RNA. These domains also contribute to bind single- and double-stranded DNA and have a duplex-stabilizing effect. However, the peptide containing the zinc finger situated towards the C-terminal end of C2-L1Tc protein has a slight destabilization effect on a mismatched DNA duplex and shows a strong preference for single-stranded nucleic acids, such as C2-L1Tc. These results provide further insight into the essential properties of the C2-L1Tc protein as a NAC.

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8

Bartas, Martin, Jiří Červeň, Simona Guziurová, Kristyna Slychko, and Petr Pečinka. "Amino Acid Composition in Various Types of Nucleic Acid-Binding Proteins." International Journal of Molecular Sciences 22, no. 2 (January 18, 2021): 922. http://dx.doi.org/10.3390/ijms22020922.

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Nucleic acid-binding proteins are traditionally divided into two categories: With the ability to bind DNA or RNA. In the light of new knowledge, such categorizing should be overcome because a large proportion of proteins can bind both DNA and RNA. Another even more important features of nucleic acid-binding proteins are so-called sequence or structure specificities. Proteins able to bind nucleic acids in a sequence-specific manner usually contain one or more of the well-defined structural motifs (zinc-fingers, leucine zipper, helix-turn-helix, or helix-loop-helix). In contrast, many proteins do not recognize nucleic acid sequence but rather local DNA or RNA structures (G-quadruplexes, i-motifs, triplexes, cruciforms, left-handed DNA/RNA form, and others). Finally, there are also proteins recognizing both sequence and local structural properties of nucleic acids (e.g., famous tumor suppressor p53). In this mini-review, we aim to summarize current knowledge about the amino acid composition of various types of nucleic acid-binding proteins with a special focus on significant enrichment and/or depletion in each category.

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9

Cai, Xiaomeng, Rui Dou, Chen Guo, Jiaruo Tang, Xiajuan Li, Jun Chen, and Jiayu Zhang. "Cationic Polymers as Transfection Reagents for Nucleic Acid Delivery." Pharmaceutics 15, no. 5 (May 15, 2023): 1502. http://dx.doi.org/10.3390/pharmaceutics15051502.

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Nucleic acid therapy can achieve lasting and even curative effects through gene augmentation, gene suppression, and genome editing. However, it is difficult for naked nucleic acid molecules to enter cells. As a result, the key to nucleic acid therapy is the introduction of nucleic acid molecules into cells. Cationic polymers are non-viral nucleic acid delivery systems with positively charged groups on their molecules that concentrate nucleic acid molecules to form nanoparticles, which help nucleic acids cross barriers to express proteins in cells or inhibit target gene expression. Cationic polymers are easy to synthesize, modify, and structurally control, making them a promising class of nucleic acid delivery systems. In this manuscript, we describe several representative cationic polymers, especially biodegradable cationic polymers, and provide an outlook on cationic polymers as nucleic acid delivery vehicles.

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10

Huang, Zhen, Andrey Kovalevsky, Qianwei Zhao, and Lillian Hu. "Nucleic acid protein crystallography facilitated by selenium nucleic acids (SeNA)." Acta Crystallographica Section A Foundations and Advances 75, a1 (July 20, 2019): a158. http://dx.doi.org/10.1107/s0108767319098428.

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11

Corey, David R. "Peptide nucleic acids: Expanding the scope of nucleic acid recognition." Trends in Biotechnology 15, no. 6 (June 1997): 224–29. http://dx.doi.org/10.1016/s0167-7799(97)01037-8.

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12

Lesk, V. I., and A. M. Lesk. "Schematic diagrams of nucleic acids and protein–nucleic acid complexes." Journal of Applied Crystallography 22, no. 6 (December 1, 1989): 569–71. http://dx.doi.org/10.1107/s0021889889008265.

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Simplified representations of components of nucleic acids have been designed and implemented as programs integrated with other software that draws schematic diagrams of proteins. Examples illustrating the structures of oligonucleotides, tRNA and a protein–nucleic acid complex indicate the utility of these representations for making intelligible illustrations of complex structures containing nucleic acids.

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13

Arnberg, A. C. "Electron microscopy of nucleic acids and protein-nucleic acid complexes." Ultramicroscopy 31, no. 4 (December 1989): 457–58. http://dx.doi.org/10.1016/0304-3991(89)90344-6.

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14

Veedu, Rakesh N, and Jesper Wengel. "Locked Nucleic Acids: Promising Nucleic Acid Analogs for Therapeutic Applications." Chemistry & Biodiversity 7, no. 3 (March 2010): 536–42. http://dx.doi.org/10.1002/cbdv.200900343.

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15

Wolcott, M. J. "Advances in nucleic acid-based detection methods." Clinical Microbiology Reviews 5, no. 4 (October 1992): 370–86. http://dx.doi.org/10.1128/cmr.5.4.370.

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Laboratory techniques based on nucleic acid methods have increased in popularity over the last decade with clinical microbiologists and other laboratory scientists who are concerned with the diagnosis of infectious agents. This increase in popularity is a result primarily of advances made in nucleic acid amplification and detection techniques. Polymerase chain reaction, the original nucleic acid amplification technique, changed the way many people viewed and used nucleic acid techniques in clinical settings. After the potential of polymerase chain reaction became apparent, other methods of nucleic acid amplification and detection were developed. These alternative nucleic acid amplification methods may become serious contenders for application to routine laboratory analyses. This review presents some background information on nucleic acid analyses that might be used in clinical and anatomical laboratories and describes some recent advances in the amplification and detection of nucleic acids.

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16

Li, Yalin, Suxiang Chen, Nan Liu, Lixia Ma, Tao Wang, Rakesh N. Veedu, Tao Li, et al. "A systematic investigation of key factors of nucleic acid precipitation toward optimized DNA/RNA isolation." BioTechniques 68, no. 4 (April 2020): 191–99. http://dx.doi.org/10.2144/btn-2019-0109.

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Nucleic acid precipitation is important for virtually all molecular biology investigations. However, despite its crucial role, a systematic study of the influence factors of nucleic acid precipitation has not been reported. In the present work, via rational experimental design, key factors of nucleic acid precipitation, including the type of nucleic acid, temperature and time of incubation, speed and time of centrifugation, volume ratio of ethanol/isopropanol to nucleic acid solution, type of cation-containing salt solution and type of coprecipitator, were comprehensively evaluated in an attempt to maximize the efficiency of nucleic acid precipitation. Our results indicate that the optimal conditions of each influence factor of nucleic acid precipitation may vary in accordance with the chemistry, structure and length of nucleic acids.

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17

Mishra, Chinmoy, and Lipismita Samal. "Peptide Nucleic Acid." Acta Informatica Medica 19, no. 2 (2011): 118. http://dx.doi.org/10.5455/aim.2011.19.118-123.

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18

Wagenknecht, Hans-Achim. "Nucleic acid chemistry." Beilstein Journal of Organic Chemistry 10 (December 10, 2014): 2928–29. http://dx.doi.org/10.3762/bjoc.10.311.

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19

Hamill, B. J. "Nucleic Acid Cookbook." Bio/Technology 3, no. 8 (August 1985): 744. http://dx.doi.org/10.1038/nbt0885-744.

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20

Vogel, F. R., and N. Sarver. "Nucleic acid vaccines." Clinical Microbiology Reviews 8, no. 3 (July 1995): 406–10. http://dx.doi.org/10.1128/cmr.8.3.406.

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The use of nucleic acid-based vaccines is a novel approach to immunization that elicits immune responses similar to those induced by live, attenuated vaccines. Administration of nucleic acid vaccines results in the endogenous generation of viral proteins with native conformation, glycosylation profiles, and other posttranslational modifications that mimic antigen produced during natural viral infection. Nucleic acid vaccines have been shown to elicit both antibody and cytotoxic T-lymphocyte responses to diverse protein antigens. Advantages of nucleic acid-based vaccines include the simplicity of the vector, the ease of delivery, the duration of expression, and, to date, the lack of evidence of integration. Further studies are needed to assess the feasibility, safety, and efficacy of this new and promising technology.

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21

Vogel, F. R., and N. Sarver. "Nucleic acid vaccines." Clinical microbiology reviews 8, no. 3 (1995): 406–10. http://dx.doi.org/10.1128/cmr.8.3.406-410.1995.

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22

Roth, Charles M., and Martin L. Yarmush. "Nucleic Acid Biotechnology." Annual Review of Biomedical Engineering 1, no. 1 (August 1999): 265–97. http://dx.doi.org/10.1146/annurev.bioeng.1.1.265.

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23

Zhirnov, Victor, Reza M. Zadegan, Gurtej S. Sandhu, George M. Church, and William L. Hughes. "Nucleic acid memory." Nature Materials 15, no. 4 (March 23, 2016): 366–70. http://dx.doi.org/10.1038/nmat4594.

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24

Liebhaber, S. A. "Nucleic Acid Degradation." Science 262, no. 5135 (November 5, 1993): 924–25. http://dx.doi.org/10.1126/science.262.5135.924-a.

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25

Carola, Christophe, and Fritz Eckstein. "Nucleic acid enzymes." Current Opinion in Chemical Biology 3, no. 3 (June 1999): 274–83. http://dx.doi.org/10.1016/s1367-5931(99)80043-x.

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26

Gilmartin, P. M. "Nucleic Acid Hybridization." Journal of Steroid Biochemistry and Molecular Biology 64, no. 5-6 (March 1998): 315–16. http://dx.doi.org/10.1016/s0960-0760(96)00244-0.

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27

Hogan, Michelle. "Nucleic Acid Testing." Nephrology Times 5, no. 8 (August 2012): 8–9. http://dx.doi.org/10.1097/01.nep.0000419369.61121.5c.

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28

Christopoulos, Theodore K. "Nucleic Acid Analysis." Analytical Chemistry 71, no. 18 (September 1999): 425–38. http://dx.doi.org/10.1021/a19900161.

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29

Toulmé, Jean-Jacques, Eric Peyrin, and Frédéric Ducongé. "Nucleic acid aptamers." Methods 97 (March 2016): 1–2. http://dx.doi.org/10.1016/j.ymeth.2016.02.015.

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30

Shugar, David. "Nucleic acid hybridization." FEBS Letters 206, no. 1 (September 29, 1986): 168. http://dx.doi.org/10.1016/0014-5793(86)81363-1.

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31

Huynh-Dinh, T. "Nucleic acid chemistry." Biochimie 74, no. 6 (June 1992): 591. http://dx.doi.org/10.1016/0300-9084(92)90166-c.

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32

Williamson, R. "Nucleic Acid Hybridisation." Journal of Clinical Pathology 39, no. 4 (April 1, 1986): 468. http://dx.doi.org/10.1136/jcp.39.4.468-a.

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33

Wells, M. "Nucleic Acid Probes." Journal of Clinical Pathology 43, no. 10 (October 1, 1990): 879. http://dx.doi.org/10.1136/jcp.43.10.879-e.

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34

Horton, Brendan. "Nucleic acid testing." Nature 390, no. 6658 (November 1997): 425–26. http://dx.doi.org/10.1038/37169.

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35

Spier, R. E. "Nucleic acid vaccines." Vaccine 13, no. 1 (January 1995): 131–32. http://dx.doi.org/10.1016/0264-410x(95)80029-d.

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36

Norton, Brendan. "Nucleic acid update." Nature 373, no. 6512 (January 1995): 366–68. http://dx.doi.org/10.1038/373366a0.

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37

Smith, W. "Nucleic acid models." Progress in Polymer Science 21, no. 2 (1996): 209–53. http://dx.doi.org/10.1016/0079-6700(95)00017-8.

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38

Waine, G. J. "Nucleic acid vaccines." Parasitology Today 10, no. 12 (January 1994): 453–54. http://dx.doi.org/10.1016/0169-4758(94)90150-3.

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39

Wang, Qi, Lei Chen, Yitao Long, He Tian, and Junchen Wu. "Molecular Beacons of Xeno-Nucleic Acid for Detecting Nucleic Acid." Theranostics 3, no. 6 (2013): 395–408. http://dx.doi.org/10.7150/thno.5935.

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40

Berman, Helen M., Christine Zardecki, and John Westbrook. "The Nucleic Acid Database: A Resource for Nucleic Acid Science." Acta Crystallographica Section D Biological Crystallography 54, no. 6 (November 1, 1998): 1095–104. http://dx.doi.org/10.1107/s0907444998007926.

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The Nucleic Acid Database (NDB) distributes information about nucleic acid-containing structures. Here the information content of the database as well as the query capabilities are described. A summary of how the technology developed by this project has been used to develop other macromolecular databases is given.

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41

Jancik Prochazkova, A., S. Gaidies, C. Yumusak, O. Brüggemann, M. Weiter, N. S. Sariciftci, M. C. Scharber, et al. "Peptide nucleic acid stabilized perovskite nanoparticles for nucleic acid sensing." Materials Today Chemistry 17 (September 2020): 100272. http://dx.doi.org/10.1016/j.mtchem.2020.100272.

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42

Berman, Helen M., Anke Gelbin, and John Westbrook. "Nucleic acid crystallography: A view from the nucleic acid database." Progress in Biophysics and Molecular Biology 66, no. 3 (January 1996): 255–88. http://dx.doi.org/10.1016/s0079-6107(97)00019-9.

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43

Koo, Bonwoo, Haneul Yoo, Ho Jeong Choi, Min Kim, Cheoljae Kim, and Ki Tae Kim. "Visible Light Photochemical Reactions for Nucleic Acid-Based Technologies." Molecules 26, no. 3 (January 21, 2021): 556. http://dx.doi.org/10.3390/molecules26030556.

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The expanding scope of chemical reactions applied to nucleic acids has diversified the design of nucleic acid-based technologies that are essential to medicinal chemistry and chemical biology. Among chemical reactions, visible light photochemical reaction is considered a promising tool that can be used for the manipulations of nucleic acids owing to its advantages, such as mild reaction conditions and ease of the reaction process. Of late, inspired by the development of visible light-absorbing molecules and photocatalysts, visible light-driven photochemical reactions have been used to conduct various molecular manipulations, such as the cleavage or ligation of nucleic acids and other molecules as well as the synthesis of functional molecules. In this review, we describe the recent developments (from 2010) in visible light photochemical reactions involving nucleic acids and their applications in the design of nucleic acid-based technologies including DNA photocleaving, DNA photoligation, nucleic acid sensors, the release of functional molecules, and DNA-encoded libraries.

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44

Wang, Xin, Yuancong Xu, Nan Cheng, Xinxian Wang, Kunlun Huang, and Yunbo Luo. "Recent Advances in Nucleic Acid Modulation for Functional Nanozyme." Catalysts 11, no. 5 (May 17, 2021): 638. http://dx.doi.org/10.3390/catal11050638.

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Nanozymes have the potential to replace natural enzymes, so they are widely used in energy conversion technologies such as biosensors and signal transduction (converting biological signals of a target into optical, electrical, or metabolic signals). The participation of nucleic acids leads nanozymes to produce richer interface effects and gives energy conversion events more attractive characteristics, creating what are called “functional nanozymes”. Since different nanozymes have different internal structures and external morphological characteristics, functional modulation needs to be compatible with these properties, and attention needs to be paid to the influence of nucleic acids on nanozyme activity. In this review, “functional nanozymes” are divided into three categories, (nanozyme precursor ion)/ (nucleic acid) self-assembly, nanozyme-nucleic acid irreversible binding, and nanozyme-nucleic acid reversible binding, and the effects of nucleic acids on modulation principles are summarized. Then, the latest developments of nucleic acid-modulated nanozymes are reviewed in terms of their use in energy conversion technology, and their conversion mechanisms are critically discussed. Finally, we outline the advantages and limitations of “functional nanozymes” and discuss the future development prospects and challenges in this field.

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45

Driscoll, Julia, Piyush Gondaliya, and Tushar Patel. "Tunneling Nanotube-Mediated Communication: A Mechanism of Intercellular Nucleic Acid Transfer." International Journal of Molecular Sciences 23, no. 10 (May 14, 2022): 5487. http://dx.doi.org/10.3390/ijms23105487.

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Tunneling nanotubes (TNTs) are thin, F-actin-based membranous protrusions that connect distant cells and can provide e a novel mechanism for intercellular communication. By establishing cytoplasmic continuity between interconnected cells, TNTs enable the bidirectional transfer of nuclear and cytoplasmic cargo, including organelles, nucleic acids, drugs, and pathogenic molecules. TNT-mediated nucleic acid transfer provides a unique opportunity for donor cells to directly alter the genome, transcriptome, and metabolome of recipient cells. TNTs have been reported to transport DNA, mitochondrial DNA, mRNA, viral RNA, and non-coding RNAs, such as miRNA and siRNA. This mechanism of transfer is observed in physiological as well as pathological conditions, and has been implicated in the progression of disease. Herein, we provide a concise overview of TNTs’ structure, mechanisms of biogenesis, and the functional effects of TNT-mediated intercellular transfer of nucleic acid cargo. Furthermore, we highlight the potential translational applications of TNT-mediated nucleic acid transfer in cancer, immunity, and neurological diseases.

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46

Kricka, Larry J., and Paolo Fortina. "Analytical Ancestry: “Firsts” in Fluorescent Labeling of Nucleosides, Nucleotides, and Nucleic Acids." Clinical Chemistry 55, no. 4 (April 1, 2009): 670–83. http://dx.doi.org/10.1373/clinchem.2008.116152.

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Abstract Background: The inherent fluorescent properties of nucleosides, nucleotides, and nucleic acids are limited, and thus the need has arisen for fluorescent labeling of these molecules for a variety of analytical applications. Content: This review traces the analytical ancestry of fluorescent labeling of nucleosides, nucleotides, and nucleic acids, with an emphasis on the first to publish or patent. The scope of labeling includes (a) direct labeling by covalent labeling of nucleic acids with a fluorescent label or noncovalent binding or intercalation of a fluorescent dye to nucleic acids and (b) indirect labeling via covalent attachment of a secondary label to a nucleic acid, and then binding this to a fluorescently labeled ligand binder. An alternative indirect strategy involves binding of a nucleic acid to a nucleic acid binder molecule (e.g., antibody, antibiotic, histone, antibody, nuclease) that is labeled with a fluorophore. Fluorescent labels for nucleic acids include organic fluorescent dyes, metal chelates, carbon nanotubes, quantum dots, gold particles, and fluorescent minerals. Summary: Fluorescently labeled nucleosides, nucleotides, and nucleic acids are important types of reagents for biological assay methods and underpin current methods of chromosome analysis, gel staining, DNA sequencing and quantitative PCR. Although these methods use predominantly organic fluorophores, new types of particulate fluorophores in the form of nanoparticles, nanorods, and nanotubes may provide the basis of a new generation of fluorescent labels and nucleic acid detection methods.

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47

Whangbo, Jennifer, Marshall Thomas, Geoffrey McCrossan, Aaron Deutsch, Kimberly Martinod, Michael Walch, and Judy Lieberman. "Binding Of Immune Serine Proteases To Nucleic Acids Enhances Their Nuclear Localization and Promotes Their Cleavage Of Nucleic Acid-Binding Protein Substrates." Blood 122, no. 21 (November 15, 2013): 3471. http://dx.doi.org/10.1182/blood.v122.21.3471.3471.

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Abstract When released from cytotoxic T lymphocytes and natural killer cells, Granzyme (Gzm) serine proteases induce programmed cell death of pathogen-infected cells and tumor cells. The Gzms rapidly accumulate in the target cell nucleus by an unknown mechanism. Many of the known substrates of GzmA and GzmB, the most abundant killer cell proteases, bind to DNA or RNA. Gzm substrates predicted by unbiased proteomics studies are also highly enriched for nucleic acid binding proteins. Here we show by fluorescence polarization assays that Gzms bind DNA and RNA with nanomolar affinity. We hypothesized that Gzm binding to nucleic acids enhances nuclear accumulation in target cells and facilitates their cleavage of nucleic acid-binding substrates. In fact, RNase treatment of cell lysates reduced cleavage of RNA binding protein (RBP) targets by GzmA and GzmB. Moreover, adding RNA to recombinant RBP substrates greatly enhanced in vitro cleavage by GzmB, but adding RNA to non-nucleic acid binding proteins did not. For example, exogenous RNA enhanced GzmB cleavage of recombinant hnRNP C1 (an RBP) but not LMNB1 (a non-RBP). In addition, GzmB cleaved the RNA-binding HuR protein efficiently only when it was bound to an HuR-binding RNA oligonucleotide, but not in the presence of an equal amount of non-binding RNA. Thus, nucleic acids facilitate Gzm cleavage of nucleic acid binding substrates. To evaluate whether nucleic acid binding influences Gzm trafficking in target cells, we incubated fixed target cells with RNase and then added Gzms. RNA degradation in target cells reduced Gzm cytosolic localization and increased nuclear accumulation. Similarly, pre-incubating Gzms with exogenous competitor DNA reduced Gzm nuclear localization. The Gzms form a monophyletic clade with other immune serine proteases including neutrophil elastase (NE) and cathepsin G (CATG). Upon neutrophil activation, NE translocates to the nucleus to drive the formation of neutrophil extracellular traps (NETs). NE and CATG, but not non-immune serine proteases such as trypsin and pancreatic elastase, also bind DNA with high affinity and localize to the nucleus of permeabilized cells. Consistent with this finding, competitor DNA also blocks the nuclear localization of NE. Moreover NE and CATG localization to NETs depends on DNA binding. Thus the antimicrobial activity of NETs may depend in part upon the affinity of these proteases for DNA. Our findings indicate that high affinity nucleic acid binding is a conserved and functionally important property of serine proteases involved in cell-mediated immunity. Disclosures: Lieberman: Alnylam Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees.

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48

Bentham Science Publisher, Bentham Science Publisher. "Nucleic Acids Modulate Autoimmunity Through Nucleic-Acid-Specific Toll-Like Receptors." Current Medicinal Chemistry 13, no. 25 (October 1, 2006): 3061–67. http://dx.doi.org/10.2174/092986706778521832.

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49

Astakhova, I. Kira, and Jesper Wengel. "Scaffolding along Nucleic Acid Duplexes Using 2′-Amino-Locked Nucleic Acids." Accounts of Chemical Research 47, no. 6 (April 21, 2014): 1768–77. http://dx.doi.org/10.1021/ar500014g.

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Koch, T. "Locked nucleic acids: a family of high affinity nucleic acid probes." Journal of Physics: Condensed Matter 15, no. 18 (April 28, 2003): S1861—S1871. http://dx.doi.org/10.1088/0953-8984/15/18/317.

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