A Pumilio-induced RNA structure switch in p27-3′2 UTR controls miR-221 and miR-222 accessibility

Martijn Kedde*, Marieke Van Kouwenhove, Wilbert Zwart, Joachim A.F. Oude Vrielink, Ran Elkon, Reuven Agami

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

332 Scopus citations

Abstract

Key regulators of 3′2 untranslated regions (3′2 UTRs) are microRNAs and RNA-binding proteins (RBPs). The p27 tumour suppressor is highly expressed in quiescent cells, and its downregulation is required for cell cycle entry after growth factor stimulation. Intriguingly, p27 accumulates in quiescent cells despite high levels of its inhibitors miR-221 and miR-222 (Refs 5, 6). Here we show that miR-221 and miR-222 are underactive towards p27-3′2 UTR in quiescent cells, as a result of target site hindrance. Pumilio-1 (PUM1) is a ubiquitously expressed RBP that was shown to interact with p27-3′2 UTR. In response to growth factor stimulation, PUM1 is upregulated and phosphorylated for optimal induction of its RNA-binding activity towards the p27-3′2 UTR. PUM1 binding induces a local change in RNA structure that favours association with miR-221 and miR-222, efficient suppression of p27 expression, and rapid entry to the cell cycle. We have therefore uncovered a novel RBP-induced structural switch modulating microRNA-mediated gene expression regulation.

Original languageEnglish
Pages (from-to)1014-1020
Number of pages7
JournalNature Cell Biology
Volume12
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Dive into the research topics of 'A Pumilio-induced RNA structure switch in p27-3′2 UTR controls miR-221 and miR-222 accessibility'. Together they form a unique fingerprint.

Cite this