Long-lived microRNA - Argonaute complexes in quiescent cells can be activated to regulate mitogenic responses

Scott H. Olejniczak, Gaspare La Rocca, Joshua J. Gruber, Craig B. Thompson

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Cellular proliferation depends on the integration of mitogenic stimuli with environmental conditions. Increasing evidence suggests that microRNAs play a regulatory role in this integration. Here we show that during periods of cellular quiescence, mature microRNAs are stabilized and stored in Argonaute protein complexes that can be activated by mitogenic stimulation to repress mitogen-stimulated targets, thus influencing subsequent cellular responses. In quiescent cells, the majority of microRNAs exist in low molecular weight, Argonaute protein-containing complexes devoid of essential components of the RNA-induced silencing complex (RISC). For at least 3 wk, this pool of Argonaute-associated microRNAs is stable and can be recruited into RISC complexes subsequent to mitogenic stimulation. Using several model systems, we demonstrate that stable Argonaute protein-associated small RNAs are capable of repressing mitogen-induced transcripts. Therefore, mature microRNAs may represent a previously unappreciated form of cellular memory that allows cells to retain posttranscriptional regulatory information over extended periods of cellular quiescence.

Original languageEnglish (US)
Pages (from-to)157-162
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number1
DOIs
StatePublished - Jan 2 2013
Externally publishedYes

Keywords

  • Ago2
  • GW182
  • Signaling

ASJC Scopus subject areas

  • General

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