Regulation of microRNA-mediated gene silencing by microRNA precursors. (Nat Struct Mol Biol. 2014 Aug 3.)

報告日期: 2014/10/31
報告時間: 3:10/4:00
報告學生: 賴輝寰(以英文報告)
講評老師: 陳百昇
附件下載: 下載[1423-1412163671-1.pdf] 

Regulation of microRNA-mediated gene silencing by microRNA precursors.

Roy-Chaudhuri B, Valdmanis PN, Zhang Y, Wang Q, Luo QJ, Kay MA

Nat Struct Mol Biol. 2014 Sep; 21(9):825-32

Speaker: Lai, Hui-Huang                                     Time: 2014/04/11, 15:10~16:00

Commentator: Professor Liu, Hsiao-Sheng         Location: Room 602

 

Abstract

MicroRNAs (miRNAs) are endogenous short single strand RNA (~22 nucleotides) that have emerged as important regulators of gene expression.MiRNA genes are transcribed by either RNA polymerase II or RNA polymerase III into long primary transcripts (primiRNAs) with folding the short hairpin secondary structure. The pri-miRNA as a substrate is cleaved by the RNase III enzyme Drosha in the nucleus to become precursor miRNA (pre-miRNAs). The ~70 nucleotides pre-miRNA with a 3 overhang which is recognized by exportin 5 protein for exporting to the cytoplasm. In the cytoplasm the RNase III enzyme Dicer processes pre-miRNAs to a ~20 bp miRNA duplex, further are separated by helicase into a functional guide strand (mature miRNA) which is complementary to the target. The mature miRNA incorporated into the miRNA induced silencing complex (miRISC) which guides the miRNA targeting the messenger RNAs by complement to its 3UTRs to repress translation, destabilized or degraded the mRNAs (1).Pri-miR-151 is subject to RNA editing that converts adenosine to inosine (A-I RNA editing) by ADAR (dsRNA-specific adenosine deaminase). RNA editing of pri-miR-151 results in complete blockage of its cleavage by Dicer and accumulation of edited pre-miR-151 (2). The authors show that miRNA precursors act as a new class of post-transcriptional regulators of miRNA activity. Pre-miR-151 can bind to and compete with mature miR-151-5p and miR-151-3p for binding sites contained within the complementary regions of the E2f6 mRNA 3UTR. Thus, these evidence provide us a new information that miRNA precursors can serve as post-transcriptional regulators of miRNA activity and are not mere biogenesis intermediates.

References

  1. Krol, J., Loedige, I., and Filipowicz, W. (2010) The widespread regulation of microRNA biogenesis, function and decay. Nature reviews. Genetics11, 597-610
  2. Kawahara, Y., Zinshteyn, B., Chendrimada, T. P., Shiekhattar, R., and Nishikura, K.

(2007) RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-

TRBP complex. EMBO reports8, 763-769