Ribonuclease

ribonuclease

Ustilago sphaerogena Ribonuclease U2 with AMP PDB entry 3agn[1]
Identifiers
Symbol Ribonuclease
Pfam PF00545
InterPro IPR000026
SCOP 1brn
SUPERFAMILY 1brn

Ribonuclease (commonly abbreviated RNase) is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 (for the phosphorolytic enzymes) and 3.1 (for the hydrolytic enzymes) classes of enzymes.

Function

All organisms studied contain many RNases of many different classes, showing that RNA degradation is a very ancient and important process. As well as cleaning of cellular RNA that is no longer required, RNases play key roles in the maturation of all RNA molecules, both messenger RNAs that carry genetic material for making proteins, and non-coding RNAs that function in varied cellular processes. In addition, active RNA degradation systems are a first defense against RNA viruses, and provide the underlying machinery for more advanced cellular immune strategies such as RNAi.

Some cells also secrete copious quantities of non-specific RNases such as A and T1. RNases are, therefore, extremely common, resulting in very short lifespans for any RNA that is not in a protected environment. It is worth noting that all intracellular RNAs are protected from RNase activity by a number of strategies including 5' end capping, 3' end polyadenylation, and folding within an RNA protein complex (ribonucleoprotein particle or RNP).

Another mechanism of protection is ribonuclease inhibitor (RI), which comprises a relatively large fraction of cellular protein (~0.1%) in some cell types, and which binds to certain ribonucleases with the highest affinity of any protein-protein interaction; the dissociation constant for the RI-RNase A complex is ~20 fM under physiological conditions. RI is used in most laboratories that study RNA to protect their samples against degradation from environmental RNases.

Similar to restriction enzymes, which cleave highly specific sequences of double-stranded DNA, a variety of endoribonucleases that recognize and cleave specific sequences of single-stranded RNA have been recently classified.

RNases play a critical role in many biological processes, including angiogenesis and self-incompatibility in flowering plants (angiosperms).[2][3] Many stress-response toxins of prokaryotic toxin-antitoxin systems have been shown to have RNase activity and homology.[4]

Classification

Major types of endoribonucleases

Structure of RNase A

Major types of exoribonucleases

RNase specificity

The active site looks like a rift valley where all the active side residues create the wall and bottom of the valley. the rift is very thin and the small substrate fits perfectly in the middle of the active site, which allows for perfect interaction with the residues. It actually has a little curvature to the site which the substrate also has. Although, usually most of exo- and endoribonucleases are not sequence specific, recently CRISPR/Cas system natively recognizing and cutting DNA was engineered to cleave ssRNA in sequence specific manner.[9]

RNase contamination during RNA extraction

The extraction of RNA in molecular biology experiments is greatly complicated by the presence of ubiquitous and hardy ribonucleases that degrade RNA samples. Certain RNases can be extremely hardy and inactivating them is difficult compared to neutralizing DNases. In addition to the cellular RNases that are released, there are several RNases that are present in the environment. RNases have evolved to have many extracellular functions in various organisms.[10][11][12] For example, RNase 7, a member of the RNase A superfamily, is secreted by human skin and serves as a potent antipathogen defence.[13][14] In these secreted RNases, the enzymatic RNase activity may not even be necessary for its new, exapted function. For example, immune RNases act by destabilizing the cell membranes of bacteria.[15][16]

References

  1. ↑ Noguchi, Shuji (2010). "Isomerization mechanism of aspartate to isoaspartate implied by structures ofUstilago sphaerogenaribonuclease U2 complexed with adenosine 3′-monophosphate". Acta Crystallographica Section D Biological Crystallography 66 (7): 843–849. doi:10.1107/S0907444910019621. ISSN 0907-4449.
  2. ↑ Michael B. Sporn; Anita B. Roberts (6 December 2012). Peptide Growth Factors and Their Receptors II. Springer Science & Business Media. p. 556. ISBN 978-3-642-74781-6.
  3. ↑ V. Raghavan (6 December 2012). Developmental Biology of Flowering Plants. Springer Science & Business Media. p. 237. ISBN 978-1-4612-1234-8.
  4. ↑ Rosenberg, Susan M.; Ramage, Holly R.; Connolly, Lynn E.; Cox, Jeffery S. (2009). "Comprehensive Functional Analysis of Mycobacterium tuberculosis Toxin-Antitoxin Systems: Implications for Pathogenesis, Stress Responses, and Evolution". PLoS Genetics 5 (12): e1000767. doi:10.1371/journal.pgen.1000767. ISSN 1553-7404.
  5. ↑ Cuchillo, C. M.; Nogués, M. V.; Raines, R. T. (2011). "Bovine pancreatic ribonuclease: Fifty years of the first enzymatic reaction mechanism". Biochemistry 50: 7835–7841. doi:10.1021/bi201075b. PMC 3172371. PMID 21838247.
  6. ↑
  7. ↑ Nowotny, Marcin (2009). "Retroviral integrase superfamily: the structural perspective". EMBO Reports 10 (2): 144–151. doi:10.1038/embor.2008.256. ISSN 1469-221X.
  8. ↑ J. Holzmann, P. Frank, E. Löffler, K. Bennett, C. Gerner & W. Rossmanith (2008). "RNase P without RNA: Identification and functional reconstitution of the human mitochondrial tRNA processing enzyme". Cell 135 (3): 462–474. doi:10.1016/j.cell.2008.09.013. PMID 18984158.
  9. ↑ Tamulaitis, Gintautas; Kazlauskiene, Migle; Manakova, Elena; Venclovas, Česlovas; Nwokeoji, Alison O.; Dickman, Mark J.; Horvath, Philippe; Siksnys, Virginijus (2014). "Programmable RNA Shredding by the Type III-A CRISPR-Cas System of Streptococcus thermophilus". Molecular Cell 56 (4): 506–517. doi:10.1016/j.molcel.2014.09.027. ISSN 1097-2765.
  10. ↑ Rossier, O.; Dao, J.; Cianciotto, N. P. (2009). "A type II secreted RNase of Legionella pneumophila facilitates optimal intracellular infection of Hartmannella vermiformis". Microbiology 155 (3): 882–890. doi:10.1099/mic.0.023218-0.
  11. ↑ Luhtala, N.; Parker, R. (2010). "T2 Family ribonucleases: Ancient enzymes with diverse roles". Trends in Biochemical Sciences 35 (5): 253–259. doi:10.1016/j.tibs.2010.02.002.
  12. ↑ Dyer, K. D.; Rosenberg, H. F. (2006). "The RNase a superfamily: Generation of diversity and innate host defense". Molecular Diversity 10 (4): 585–597. doi:10.1007/s11030-006-9028-2.
  13. ↑ Harder, J. (2002). "RNase 7, a Novel Innate Immune Defense Antimicrobial Protein of Healthy Human Skin". Journal of Biological Chemistry 277 (48): 46779–46784. doi:10.1074/jbc.M207587200.
  14. ↑ Köten, B.; Simanski, M.; Gläser, R.; Podschun, R.; Schröder, J. M.; Harder, J. R. (2009). "RNase 7 Contributes to the Cutaneous Defense against Enterococcus faecium". PLoS ONE 4 (7): e6424. doi:10.1371/journal.pone.0006424.
  15. ↑ Huang, Y. -C.; Lin, Y. -M.; Chang, T. -W.; Wu, S. -J.; Lee, Y. -S.; Chang, M. D. -T.; Chen, C.; Wu, S. -H.; Liao, Y. -D. (2006). "The Flexible and Clustered Lysine Residues of Human Ribonuclease 7 Are Critical for Membrane Permeability and Antimicrobial Activity". Journal of Biological Chemistry 282 (7): 4626–4633. doi:10.1074/jbc.M607321200.
  16. ↑ Rosenberg, H. F. (2008). "RNase a ribonucleases and host defense: An evolving story". Journal of Leukocyte Biology 83 (5): 1079–87. doi:10.1189/jlb.1107725. PMC 2692241. PMID 18211964.

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External links

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