Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control.
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.
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Barsanjit
B
Mazumder
Prabha
P
Sampath
Vasudevan
V
Seshadri
Ratan K
RK
Maitra
Paul E
PE
DiCorleto
Paul L
PL
Fox
D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D002570:Ceruloplasmin / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects; D017434:Protein Structure, Tertiary; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D020298:U937 Cells
D020413:3' Untranslated Regions; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; D007371:Interferon-gamma; D002570:Ceruloplasmin