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short interfering double-stranded RNA; antisense oligonucleotide (siRNA, microRNA, miRNA)

Function: - siRNA's are 18-24 base pair double-stranded RNAs capable of inhibiting translation of mRNA (to which one of their strands is complementary) - siRNA are endogenously transcribed in normal eukaryotic cells in a regulated manner [5,6] & function to regulate translation of mRNA - the double-stranded RNA is catabolized by the cells through recruitment of a large protein complex known as the RNA-induced silencing complex, (RISC) - siRNAs are thought to regulate: [5,6] a) cellular differentiation b) proliferation c) apoptosis Biochemistry: - the 18-24 base-pair length is small enough to evade the immune response - siRNA are taken up into cells - they are degraded intracellularly, typically in 2-3 days Pharmacology: 1) siRNAs transfected into virus-infected cells may be useful for inhibiting production of viral proteins 2) transfection facilitates stable production of the siRNA 3) intranasal siRNA may inhibit respiratory virus infection 4) therapeutically relevant effects in primates [5] Genetics: - genes encoding siRNA include: - SCA8 gene (putative) Pathology: - miR-1 is overproduced in ischemic cardiac muscle when overproduced in rat hearts, miR-1 induces ectopy - miR-208 plays a role in hypertrophy of myocytes & fibrosis when the heart is stressed [9] - miR-33a & miR-33b inhibit production of HDL cholesterol [11]

Related

microRNA host gene protein (MIRH) RNA-induced silencing complex (RISC)

Specific

bepirovirsen donidalorsen eplontersen (Wainua) FXI-ASO givosiran (Givlaari) inclisiran (Leqvio, ALN-PCS) inotersen (Tegsedi) lepodisiran lumasiran (Oxlumo) miR-1 miR-126 miR-132 miR-208 miR-21 miR-33 miR-34a nedosiran (Rivfloza) olpasiran patisiran (Onpattro) vutrisiran (Amvuttra) zerlasiran

General

small non coding rna

References

  1. Journal Watch 22(16):128, 2002 Novina CD et al, siRNA-directed inhibition of HIV-1 infection Nat Med 8:681, 2002 PMID: 12042777 - Pomerantz RJ, RNA interference meets HIV-1: will silence be golden? Nat Med 8:659 2001 PMID: 12091895
  2. Sui G et al, A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5515-20. PMID: 11960009
  3. Journal Watch 24(1):9, 2004
  4. Journal Watch 25(4):29, 2005 Bitko V, Musiyenko A, Shulyayeva O, Barik S. Inhibition of respiratory viruses by nasally administered siRNA. Nat Med. 2005 Jan;11(1):50-5. Epub 2004 Dec 26. PMID: 15619632 - Zhang W, Yang H, Kong X, Mohapatra S, Juan-Vergara HS, Hellermann G, Behera S, Singam R, Lockey RF, Mohapatra SS. Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene. Nat Med. 2005 Jan;11(1):56-62. Epub 2004 Dec 26. PMID: 15619625
  5. Journal Watch 25(15):122, 2005 O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005 Jun 9;435(7043):839-43. PMID: 15944709 - Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature. 2005 Jun 9;435(7043):834-8. PMID: 15944708 - He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. A microRNA polycistron as a potential human oncogene. Nature. 2005 Jun 9;435(7043):828-33. PMID: 15944707 - Meltzer PS. Cancer genomics: small RNAs with big impacts. Nature. 2005 Jun 9;435(7043):745-6. No abstract available. PMID: 15944682
  6. Mendell JT. MicroRNAs: Critical Regulators of Development, Cellular Physiology and Malignancy. Cell Cycle. 2005 Sep 15;4(9) [Epub ahead of print] PMID: 16096373
  7. Zimmermann TS et al, RNAi-mediated gene silencing in non-human primates. Nature 2006; 441:111 PMID: 16565705
  8. Yang B, Lin H, Xiao J, Lu Y, Luo X, Li B, Zhang Y, Xu C, Bai Y, Wang H, Chen G, Wang Z. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med. 2007 Apr;13(4):486-491. Epub 2007 Apr 1. PMID: 17401374
  9. van Rooij E et al, Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007, 316:575 PMID: 17379774
  10. Kumar P et al. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 2008 Aug 22; 134:577. PMID: 18691745 http://dx.doi.org/10.1016/j.cell.2008.06.034
  11. Rayner KJ et al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature 2011 Oct 20; 478:404 PMID: 22012398
  12. Krzeszinski JY et al. miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2. Nature 2014 Aug 28; 512:431 PMID: 25043055