Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control

被引:278
作者
Mazumder, B
Sampath, P
Seshadri, V
Maitra, RK
DiCorleto, PE
Fox, PL
机构
[1] Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA
[2] Cleveland Clin Fdn, Lerner Res Inst, Virus Core Facil, Cleveland, OH 44195 USA
[3] Cleveland State Univ, Dept Biol, Cleveland, OH 44115 USA
关键词
D O I
10.1016/S0092-8674(03)00773-6
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
Transcript-specific translational control is generally directed by binding of trans-acting proteins to structural elements in the untranslated region (UTR) of the target mRNA. Here, we elucidate a translational silencing mechanism involving regulated release of an integral ribosomal protein and subsequent binding to its target mRNA. Human ribosomal protein L13a was identified as a candidate interferon-Gamma-Activated Inhibitor of Translation (GAIT) of ceruloplasmin (Cp) mRNA by a genetic screen for Cp 3' -UTR binding proteins. In vitro activity of L13a was shown by inhibition of target mRNA translation by recombinant protein. In response to interferon-gamma in vivo, the entire cellular pool of L13a was phosphorylated and released from the 60S ribosomal subunit. Released L13a specifically bound the 3'-UTR GAIT element of Cp mRNA and silenced translation. We propose a model in which the ribosome functions not only as a protein synthesis machine, but also as a depot for regulatory proteins that modulate translation.
引用
收藏
页码:187 / 198
页数:12
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