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

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