siRNAの役割

2006年ノーベル医学生理学賞

2006 Nobel Prize winner Craig Mello UMass Chan Medical School チャンネル登録者数 5760人
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The Nobel Prize in Physiology or Medicine 2006 was awarded jointly to Andrew Z. Fire and Craig C. Mello “for their discovery of RNA interference – gene silencing by double-stranded RNA”

https://www.nobelprize.org/prizes/medicine/2006/summary/

siRNAについて(およびmiRNAとの相違点）

  • The RNase III enzyme DICER is responsible for biosynthesis of short-interfering RNAs (siRNAs) and microRNAs (miRNAs).
  • DICER processes long double-stranded RNA (dsRNA) precursors into 21–23 bp-long duplexes known as siRNAs [1].
  • miRNAs are encoded by specific genomic loci and are processed from endogenous hairpin-shaped transcripts that are initially cleaved in the nucleus to a 70-bp miRNA precursor (pre-miRNA) by the Microprocessor complex, which is composed of the RNase III enzyme DROSHA and its partner,
  • Although both siRNAs and miRNAs are synthesized as duplexes, only one of the two strands, the ‘guide’ strand, is incorporated into the multi-protein complex RNA-induced silencing complex (RISC); the other strand (‘passenger’ strand) is discarded [3].
  • The guide strand recognizes a target mRNA by Watson-Crick base pairing and, based on the degree of sequence complementarity between the small RNA and target mRNA, either endonucleolytic cleavage or translational repression of the target mRNA follows [4].
  • In animals, siRNAs are perfectly complementary to their targets, and hence trigger mRNA cleavage,
  • miRNAs are usually only partially complementary and silence gene expression by translational repression and mRNA decay.
  • ARGONAUTE (AGO) proteins are at the core of RISC.
  • In mammals, there are four AGO proteins (AGO1–4). All four can bind small RNAs and trigger translational repression, but only AGO2 possesses endonucleolytic activity and is the catalytic component of RISC [6].

Essential Role for Endogenous siRNAs during Meiosis in Mouse Oocytes Paula Stein,Nikolay V. Rozhkov,Fan Li,Fabián L. Cárdenas,Olga Davydenk,Lee E. Vandivier,Brian D. Gregory,Gregory J. Hannon,Richard M. Schultz Published: February 19, 2015 https://doi.org/10.1371/journal.pgen.1005013　PLOSNEGETICS

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005013