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.

H19 long noncoding RNA controls the mRNA decay promoting function of KSRP / M. Giovarelli, G. Bucci, A. Ramos, D. Bordo, C.J. Wilusz, C. Chen, M. Puppo, P. Briata, R. Gherzi. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 111:47(2014 Nov), pp. E5023-E5028. [10.1073/pnas.1415098111]

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

M. Giovarelli
Primo
;
G. Bucci;
2014-11

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.
Long noncoding RNA; MRNA decay; RNA-binding proteins; Animals; Cell Line; Humans; Protein Binding; RNA, Long Noncoding; RNA, Messenger; RNA-Binding Proteins; Trans-Activators; Multidisciplinary
Settore BIO/11 - Biologia Molecolare
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/619521
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