Giovarelli, M;
Bucci, G;
Ramos, A;
Bordo, D;
Wilusz, CJ;
Chen, C-Y;
Puppo, M;
... Gherzi, R; + view all
(2014)
H19 long noncoding RNA controls the mRNA decay promoting function of KSRP.
PNAS - Proceedings of The National Academy of Sciences of The United States of America
, 111
(47)
E5023-E5028.
10.1073/pnas.1415098111.
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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.
| Type: | Article |
|---|---|
| Title: | H19 long noncoding RNA controls the mRNA decay promoting function of KSRP |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1073/pnas.1415098111 |
| Publisher version: | http://dx.doi.org/10.1073/pnas.1415098111 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, long noncoding RNA, mRNA decay, RNA-binding proteins, WHITE ADIPOSE-TISSUE, MUSCLE DIFFERENTIATION, SKELETAL MYOGENESIS, BINDING PROTEIN, KH DOMAINS, MICRORNAS, GENE, EXPRESSION, CANCER, HUR |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1458042 |
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