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Nat Struct Mol Biol. 2014 Jan;21(1):26-35. doi: 10.1038/nsmb.2739. Epub 2013 Dec 15.

Staufen1 senses overall transcript secondary structure to regulate translation.

Author information

1
1] Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [2] RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [3] Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
2
1] Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [2] RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [3] Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [4].

Abstract

Human Staufen1 (Stau1) is a double-stranded RNA (dsRNA)-binding protein implicated in multiple post-transcriptional gene-regulatory processes. Here we combined RNA immunoprecipitation in tandem (RIPiT) with RNase footprinting, formaldehyde cross-linking, sonication-mediated RNA fragmentation and deep sequencing to map Staufen1-binding sites transcriptome wide. We find that Stau1 binds complex secondary structures containing multiple short helices, many of which are formed by inverted Alu elements in annotated 3' untranslated regions (UTRs) or in 'strongly distal' 3' UTRs. Stau1 also interacts with actively translating ribosomes and with mRNA coding sequences (CDSs) and 3' UTRs in proportion to their GC content and propensity to form internal secondary structure. On mRNAs with high CDS GC content, higher Stau1 levels lead to greater ribosome densities, thus suggesting a general role for Stau1 in modulating translation elongation through structured CDS regions. Our results also indicate that Stau1 regulates translation of transcription-regulatory proteins.

PMID:
24336223
PMCID:
PMC4605437
DOI:
10.1038/nsmb.2739
[Indexed for MEDLINE]
Free PMC Article

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