Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 47, Pages E5023-E5028Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1415098111
Keywords
long noncoding RNA; mRNA decay; RNA-binding proteins
Categories
Funding
- Associazione Italiana per la Ricerca sul Cancro [10090]
- Association for International Cancer Research Grant [10-0527]
- Ministero della Salute [129/RF-2010-2306205]
- Medical Research Council [MC_PC_13051]
- MRC [MC_U117574558, MC_PC_13051] Funding Source: UKRI
- Medical Research Council [MC_U117574558, MC_PC_13051] Funding Source: researchfish
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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.
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