Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay

Cell. 2005 Jan 28;120(2):195-208. doi: 10.1016/j.cell.2004.11.050.

Abstract

Mammalian Staufen (Stau)1 is an RNA binding protein that is thought to function in mRNA transport and translational control. Nonsense-mediated mRNA decay (NMD) degrades abnormal and natural mRNAs that terminate translation sufficiently upstream of a splicing-generated exon-exon junction. Here we describe an mRNA decay mechanism that involves Stau1, the NMD factor Upf1, and a termination codon. Unlike NMD, this mechanism does not involve pre-mRNA splicing and occurs when Upf2 or Upf3X is downregulated. Stau1 binds directly to Upf1 and elicits mRNA decay when tethered downstream of a termination codon. Stau1 also interacts with the 3'-untranslated region of ADP-ribosylation factor (Arf)1 mRNA. Accordingly, downregulating either Stau1 or Upf1 increases Arf1 mRNA stability. These findings suggest that Arf1 mRNA is a natural target for Stau1-mediated decay, and data indicate that other mRNAs are also natural targets. We discuss this pathway as a means for cells to downregulate the expression of Stau1 binding transcripts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / metabolism*
  • ADP-Ribosylation Factor 1 / genetics
  • ADP-Ribosylation Factor 1 / metabolism*
  • Animals
  • Cells, Cultured
  • Codon, Terminator / genetics
  • Exons / genetics
  • HeLa Cells
  • Humans
  • Mice
  • RNA Helicases
  • RNA Splicing / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Two-Hybrid System Techniques

Substances

  • 3' Untranslated Regions
  • Codon, Terminator
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Stau1 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • UPF2 protein, human
  • RNA Helicases
  • UPF1 protein, human
  • ADP-Ribosylation Factor 1