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

Yoon Ki Kim; Luc Furic; Luc DesGroseillers; Lynne E. Maquat

doi:10.1016/j.cell.2004.11.050

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

Yoon Ki Kim, Luc Furic, Luc DesGroseillers, Lynne E. Maquat

Research output: Contribution to journal › Article › peer-review

415 Citations (Scopus)

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.

Original language	English
Pages (from-to)	195-208
Number of pages	14
Journal	Cell
Volume	120
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2004.11.050
Publication status	Published - 2005 Jan 28
Externally published	Yes

Bibliographical note

Funding Information:
We thank the University of Rochester Nathan Shock Proteomic Core, in particular Sarah Leistman and David Pearce, for undertaking the two-hybrid analyses; the Genome Quebec Innovation Centre, in particular Rob Sladek and André Ponton, for microarray screening and analysis; and Véronique Trépanier for technical assistance with cDNA cloning. We are grateful to Jens Lykke-Andersen for pcβ-6bs, pcβUAC-6bs, pcβ-8bs, pcNMS2, pcNMS2-Upf1, pcNMS2-Upf2, pcNMS2-Upf3, and α-Upf1 antibody; John Atkins for p2luc; Steve Burley for pGEX-6p-1+NdeI; Marv Wickens for pET-MS2; Nahum Sonenberg for α-eIF3b antibody; Michael Kiebler for α-Barentsz antibody; Juan Ortı́n for α-human Stau1 antibody; Joseph Wedekind and Trudi Schüpbach for help conversations; and Fabrice Lejeune for comments on the manuscript. This work was supported grants from the NIH to L.E.M. and grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) (to L.D.G.). L.F. was supported by scholarships from Fonds de la recherche en santé du Québec (FRSQ) and NSERC.

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.cell.2004.11.050

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@article{b8346781e08f4e65ae1ad7d7930f7c8a,

title = "Mammalian Staufen1 recruits Upf1 to specific mRNA 3′UTRs so as to elicit mRNA decay",

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.",

author = "Kim, {Yoon Ki} and Luc Furic and Luc DesGroseillers and Maquat, {Lynne E.}",

note = "Funding Information: We thank the University of Rochester Nathan Shock Proteomic Core, in particular Sarah Leistman and David Pearce, for undertaking the two-hybrid analyses; the Genome Quebec Innovation Centre, in particular Rob Sladek and Andr{\'e} Ponton, for microarray screening and analysis; and V{\'e}ronique Tr{\'e}panier for technical assistance with cDNA cloning. We are grateful to Jens Lykke-Andersen for pcβ-6bs, pcβUAC-6bs, pcβ-8bs, pcNMS2, pcNMS2-Upf1, pcNMS2-Upf2, pcNMS2-Upf3, and α-Upf1 antibody; John Atkins for p2luc; Steve Burley for pGEX-6p-1+NdeI; Marv Wickens for pET-MS2; Nahum Sonenberg for α-eIF3b antibody; Michael Kiebler for α-Barentsz antibody; Juan Ort{\'ı}n for α-human Stau1 antibody; Joseph Wedekind and Trudi Sch{\"u}pbach for help conversations; and Fabrice Lejeune for comments on the manuscript. This work was supported grants from the NIH to L.E.M. and grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) (to L.D.G.). L.F. was supported by scholarships from Fonds de la recherche en sant{\'e} du Qu{\'e}bec (FRSQ) and NSERC. ",

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doi = "10.1016/j.cell.2004.11.050",

language = "English",

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journal = "Cell",

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AU - Kim, Yoon Ki

AU - Furic, Luc

AU - DesGroseillers, Luc

AU - Maquat, Lynne E.

N1 - Funding Information: We thank the University of Rochester Nathan Shock Proteomic Core, in particular Sarah Leistman and David Pearce, for undertaking the two-hybrid analyses; the Genome Quebec Innovation Centre, in particular Rob Sladek and André Ponton, for microarray screening and analysis; and Véronique Trépanier for technical assistance with cDNA cloning. We are grateful to Jens Lykke-Andersen for pcβ-6bs, pcβUAC-6bs, pcβ-8bs, pcNMS2, pcNMS2-Upf1, pcNMS2-Upf2, pcNMS2-Upf3, and α-Upf1 antibody; John Atkins for p2luc; Steve Burley for pGEX-6p-1+NdeI; Marv Wickens for pET-MS2; Nahum Sonenberg for α-eIF3b antibody; Michael Kiebler for α-Barentsz antibody; Juan Ortı́n for α-human Stau1 antibody; Joseph Wedekind and Trudi Schüpbach for help conversations; and Fabrice Lejeune for comments on the manuscript. This work was supported grants from the NIH to L.E.M. and grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) (to L.D.G.). L.F. was supported by scholarships from Fonds de la recherche en santé du Québec (FRSQ) and NSERC.

PY - 2005/1/28

Y1 - 2005/1/28

N2 - 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.

AB - 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.

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DO - 10.1016/j.cell.2004.11.050

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AN - SCOPUS:12944327374

SN - 0092-8674

VL - 120

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JO - Cell

JF - Cell

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ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

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