The RNA Surveillance Factor UPF1 Represses Myogenesis via Its E3 Ubiquitin Ligase Activity

被引:44
作者
Feng, Qing [1 ,2 ,3 ]
Jagannathan, Sujatha [1 ,2 ,4 ]
Bradley, Robert K. [1 ,2 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Computat Biol Program, Seattle, WA 98109 USA
[2] Fred Hutchinson Canc Res Ctr, Basic Sci Div, Seattle, WA 98109 USA
[3] Univ Washington, Mol & Cellular Biol Grad Program, Seattle, WA 98105 USA
[4] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA
关键词
NONSENSE-MEDIATED DECAY; PROTEIN-QUALITY CONTROL; MESSENGER-RNA; SUBUNIT DISSOCIATION; TERMINATION CODON; GENE-EXPRESSION; DEGRADATION; RIBOSOME; DIFFERENTIATION; INHIBITION;
D O I
10.1016/j.molcel.2017.05.034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
UPF1 is an RNA helicase that orchestrates nonsense-mediated decay and other RNA surveillance pathways. While UPF1 is best known for its basal cytoprotective role in degrading aberrant RNAs, UPF1 also degrades specific, normally occurring mRNAs to regulate diverse cellular processes. Here we describe a role for UPF1 in regulated protein decay, wherein UPF1 acts as an E3 ubiquitin ligase to repress human skeletal muscle differentiation. Suppressing UPF1 accelerates myogenesis, while ectopically increasing UPF1 levels slows myogenesis. UPF1 promotes the decay of MYOD protein, a transcription factor that is a master regulator of myogenesis, while leaving MYOD mRNA stability unaffected. UPF1 acts as an E3 ligase via its RING domain to promote MYOD protein ubiquitination and degradation. Our data characterize a regulatory role for UPF1 in myogenesis, and they demonstrate that UPF1 provides a mechanistic link between the RNA and protein decay machineries in human cells.
引用
收藏
页码:239 / +
页数:19
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