Communication with the Exon-Junction complex and activation of nonsense-mediated decay by human Upf proteins occur in the cytoplasm

被引：61

作者：

Singh, Guramrit ^{[1
]}

Jakob, Steffen ^{[1
]}

Kleedehn, Mark G. ^{[1
]}

Lykke-Andersen, Jens ^{[1
]}

机构：

[1] Univ Colorado, Boulder, CO 80309 USA

来源：

MOLECULAR CELL | 2007年 / 27卷 / 05期

基金：

美国国家科学基金会;

关键词：

D O I：

10.1016/j.molcel.2007.06.030

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：

The nonsense-mediated mRNA decay (NMD) pathway rids eukaryotic cells of mRNAs with premature termination codons. There is contradictory evidence as to whether mammalian NMD is a nuclear or a cytoplasmic process. Here, we show evidence that NMD in human cells occurs primarily, if not entirely, in the cytoplasm. Polypeptides designed to inhibit interactions between NMD factors specifically impede NMD when exogenously expressed in the cytoplasm. However, restricting the polypeptides to the nucleus strongly impairs their NMD-inhibitory function, even for those intended to inhibit interactions between the exon-junction complex (EJC) and hUpf3 proteins, which localize primarily in the nucleus. NMD substrates classified based on cell fractionation assays as "nucleus associated" or "cytoplasmic" are all inhibited in the same manner. Furthermore, retention of the NMD factor hUpf1 in the nucleus strongly impairs NMD. These observations suggest that the hUpf complex communicates with the EJC and triggers NMD in the cytoplasm.

引用

页码：780 / 792

页数：13

共 60 条

[1] Nonsense mutations in the alcohol dehydrogenase gene of Drosophila melanogaster correlate with an abnormal 3′ end processing of the corresponding pre-mRNA [J].