H19 long noncoding RNA controls the mRNA decay promoting function of KSRP

Matteo Giovarelli, Gabriele Bucci, Andres Ramos, Domenico Bordo, Carol J. Wilusz, Ching Yi Chen, Margherita Puppo, Paola Briata, Roberto Gherzi

Research output: Contribution to journalArticlepeer-review

Abstract

Long noncoding RNAs (lncRNAs) interact with protein factors to regulate different layers of gene expression transcriptionally or posttranscriptionally. Here we report on the functional consequences of the unanticipated interaction of the RNA binding protein K homology-type splicing regulatory protein (KSRP) with the H19 lncRNA (H19). KSRP directly binds to H19 in the cytoplasm of undifferentiated multipotent mesenchymal C2C12 cells, and this interaction favors KSRP-mediated destabilization of labile transcripts such as myogenin. AKT activation induces KSRP dismissal from H19 and, as a consequence, myogenin mRNA is stabilized while KSRP is repurposed to promote maturation of myogenic microRNAs, thus favoring myogenic differentiation. Our data indicate that H19 operates as a molecular scaffold that facilitates effective association of KSRP with myogenin and other labile transcripts, and we propose that H19 works with KSRP to optimize an AKT-regulated posttranscriptional switch that controls myogenic differentiation.

Original languageEnglish
Pages (from-to)E5023-E5028
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number47
DOIs
Publication statusPublished - Nov 25 2014

Keywords

  • Long noncoding RNA
  • MRNA decay
  • RNA-binding proteins

ASJC Scopus subject areas

  • General

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