title: Staufen1 senses overall transcript secondary structure to regulate translation.
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.
authors: 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.
authors: Emiliano P
authors: EP
authors: Ricci
authors: 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.
authors: Alper
authors: A
authors: Kucukural
authors: 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].
authors: Can
authors: C
authors: Cenik
authors: 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.
authors: Blandine C
authors: BC
authors: Mercier
authors: 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.
authors: Guramrit
authors: G
authors: Singh
authors: 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.
authors: Erin E
authors: EE
authors: Heyer
authors: 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.
authors: Ami
authors: A
authors: Ashar-Patel
authors: 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.
authors: Lingtao
authors: L
authors: Peng
authors: 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.
authors: Melissa J
authors: MJ
authors: Moore
mesh_terms: D020413:3' Untranslated Regions; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C492185:STAU1 protein, human