Nature Structural & Molecular Biology 13, 103 - 111 (2006)
Published online: 22 January 2006; | doi:10.1038/nsmb1052
Direct ribosomal binding by a cellular inhibitor of translationDaniel A Colón-Ramos1, 5, 6, Christina L Shenvi2, 6, Douglas H Weitzel1, Eugene C Gan1, Robert Matts3, Jamie Cate2, 4, 6
& Sally Kornbluth1, 61
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. 2
Departments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. 3
Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma 74078, USA. 4
Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. 5
Present address: Department of Biological Sciences, Stanford University, Stanford, California 94305, USA. 6
These authors contributed equally to this work.
Correspondence should be addressed to Sally Kornbluth kornb001@mc.duke.edu During apoptosis and under conditions of cellular stress, several signaling pathways promote inhibition of cap-dependent translation while allowing continued translation of specific messenger RNAs encoding regulatory and stress-response proteins. We report here that the apoptotic regulator Reaper inhibits protein synthesis by binding directly to the 40S ribosomal subunit. This interaction does not affect either ribosomal association of initiation factors or formation of 43S or 48S complexes. Rather, it interferes with late initiation events upstream of 60S subunit joining, apparently modulating start-codon recognition during scanning. CrPV IRES–driven translation, involving direct ribosomal recruitment to the start site, is relatively insensitive to Reaper. Thus, Reaper is the first known cellular ribosomal binding factor with the potential to allow selective translation of mRNAs initiating at alternative start codons or from certain IRES elements. This function of Reaper may modulate gene expression programs to affect cell fate.
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