Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression.

Abstract:

:MicroRNAs are small endogenous noncoding RNAs involved in posttranscriptional gene regulation. During microRNA biogenesis, Drosha and Dicer process the primary transcript (pri-miRNA) through a precursor hairpin (pre-miRNA) to the mature miRNA. The miRNA is incorporated into the RNA-Induced Silencing Complex (RISC) with Argonaute proteins, the effector molecules in RNA interference (RNAi). Here, we show that all Argonautes elevate mature miRNA expression posttranscriptionally, independent of RNase activity. Also, we identify a role for the RISC slicer Argonaute2 (Ago2) in cleaving the pre-miRNA to an additional processing intermediate, termed Ago2-cleaved precursor miRNA or ac-pre-miRNA. This endogenous, on-pathway intermediate results from cleavage of the pre-miRNA hairpin 12 nucleotides from its 3'-end. By analogy to siRNA processing, Ago2 cleavage may facilitate removal of the nicked passenger strand from RISC after maturation. The multiple roles of Argonautes in the RNAi effector phase and miRNA biogenesis and maturation suggest coordinate regulation of microRNA expression and function.

journal_name

Cell

journal_title

Cell

authors

Diederichs S,Haber DA

doi

10.1016/j.cell.2007.10.032

subject

Has Abstract

pub_date

2007-12-14 00:00:00

pages

1097-108

issue

6

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(07)01351-7

journal_volume

131

pub_type

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