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PMID: 24470147 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Functional signature for the recognition of specific target mRNAs by human Staufen1 protein.

Nucleic acids research ·Vol. 42 ·No. 7 ·2014-04-00 ·Pages 4516-26

de Lucas S, Oliveros JC, Chagoyen M, Ortín J

Abstract

Cellular messenger RNAs (mRNAs) are associated to proteins in the form of ribonucleoprotein particles. The double-stranded RNA-binding (DRB) proteins play important roles in mRNA synthesis, modification, activity and decay. Staufen is a DRB protein involved in the localized translation of specific mRNAs during Drosophila early development. The human Staufen1 (hStau1) forms RNA granules that contain translation regulation proteins as well as cytoskeleton and motor proteins to allow the movement of the granule on microtubules, but the mechanisms of hStau1-RNA recognition are still unclear. Here we used a combination of affinity chromatography, RNAse-protection, deep-sequencing and bioinformatic analyses to identify mRNAs differentially associated to hStau1 or a mutant protein unable to bind RNA and, in this way, defined a collection of mRNAs specifically associated to wt hStau1. A common sequence signature consisting of two opposite-polarity Alu motifs was present in the hStau1-associated mRNAs and was shown to be sufficient for binding to hStau1 and hStau1-dependent stimulation of protein expression. Our results unravel how hStau1 identifies a wide spectrum of cellular target mRNAs to control their localization, expression and fate.

MeSH Terms
Alu Elements Binding Sites Cytoskeletal Proteins/metabolism HEK293 Cells Humans RNA, Messenger/chemistry,metabolism RNA-Binding Proteins/metabolism Sequence Analysis, RNA
Chemicals
Cytoskeletal Proteins RNA, Messenger RNA-Binding Proteins STAU1 protein, human
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
de Lucas Susana
Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología (CSIC), C/Darwin 3, Campus Cantoblanco, 28049 Madrid, Spain, Ciber de Enfermedades Respiratorias (ISCIII), Mallorca, Spain, Servicio de Genómica Computacional, Centro Nacional de Biotecnología (CSIC), C/Darwin 3, Campus Cantoblanco, 28049 Madrid, Spain and Bioinformática de Sistemas, Centro Nacional de Biotecnología (CSIC), C/Darwin 3, Campus Cantoblanco, 28049 Madrid, Spain.
Oliveros Juan Carlos
Chagoyen Mónica
Ortín Juan
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gku073
Published
2014-04-00
Epub
2014-00-26
Pages
4516-26
Language
English
Region
England
NLM ID
0411011
PMCID
PMC3985646
Subset
IM
Databases
GEO
GSE47226
External Links
PubMed source DOI: 10.1093/nar/gku073 PMC Full Text View journal details
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