Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
RNA. 2011 Oct;17(10):1858-69. doi: 10.1261/rna.2778911. Epub 2011 Aug 30.

Argonaute protein identity and pairing geometry determine cooperativity in mammalian RNA silencing.

Author information

  • 1University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract

Small RNAs loaded into Argonaute proteins direct silencing of complementary target mRNAs. It has been proposed that multiple, imperfectly complementary small interfering RNAs or microRNAs, when bound to the 3' untranslated region of a target mRNA, function cooperatively to silence target expression. We report that, in cultured human HeLa cells and mouse embryonic fibroblasts, Argonaute1 (Ago1), Ago3, and Ago4 act cooperatively to silence both perfectly and partially complementary target RNAs bearing multiple small RNA-binding sites. Our data suggest that for Ago1, Ago3, and Ago4, multiple, adjacent small RNA-binding sites facilitate cooperative interactions that stabilize Argonaute binding. In contrast, small RNAs bound to Ago2 and pairing perfectly to an mRNA target act independently to silence expression. Noncooperative silencing by Ago2 does not require the endoribonuclease activity of the protein: A mutant Ago2 that cannot cleave its mRNA target also silences noncooperatively. We propose that Ago2 binds its targets by a mechanism fundamentally distinct from that used by the three other mammalian Argonaute proteins.

PMID:
21878547
[PubMed - indexed for MEDLINE]
PMCID:
PMC3185918
Free PMC Article

Images from this publication.See all images (7)Free text

FIGURE 1.
FIGURE 2.
FIGURE 3.
FIGURE 4.
FIGURE 5.
FIGURE 6.
FIGURE 7.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk