PMID:14567916
| Citation |
Mazumder, B, Sampath, P, Seshadri, V, Maitra, RK, DiCorleto, PE and Fox, PL (2003) Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control. Cell 115:187-98 |
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| Abstract |
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. |
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| Keywords |
3' Untranslated Regions; Amino Acid Sequence; Ceruloplasmin/genetics; Gene Expression Regulation/drug effects; Gene Silencing; Humans; Interferon-gamma/pharmacology; Models, Biological; Models, Molecular; Molecular Sequence Data; Molecular Structure; Phosphorylation; Protein Biosynthesis/drug effects; Protein Structure, Tertiary; RNA Processing, Post-Transcriptional; RNA, Messenger/drug effects; RNA, Messenger/metabolism; Recombinant Proteins/metabolism; Ribosomal Proteins/chemistry; Ribosomal Proteins/drug effects; Ribosomal Proteins/genetics; Ribosomal Proteins/metabolism; Ribosomes/chemistry; Ribosomes/metabolism; Time Factors; U937 Cells |
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