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Mol. Cell. Biol. doi:10.1128/MCB.00019-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Ribosomal protein L33 is required for ribosome biogenesis, subunit joining and repression of GCN4 translation

Instituto de Microbiología Bioquímica, CSIC/Universidad de Salamanca, Edificio Departamental de Biología, Campus Miguel de Unamuno, 37007 Salamanca, SPAIN; Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, Bethesda, MD 20892 USA

^* To whom correspondence should be addressed. Email: tamame{at}usal.es.

	Abstract

We identified a mutation in 60S ribosomal protein L33A (rpl33a-G76R) that elicits derepression of GCN4 translation (Gcd^- phenotype) by allowing scanning preinitiation complexes to bypass the inhibitory upstream open reading frame-4 (uORF4) independent of prior uORF1 translation and reinitiation. At 37°C, rpl33a-G76R confers defects in 60S biogenesis comparable to those produced by deletion of RPL33A (A). At 28°C, however, the 60S biogenesis defect is less severe in rpl33a-G76R than in A cells, yet rpl33a-G76R confers greater derepression of GCN4 and a larger reduction in general translation. Hence, it appears that rpl33a-G76R has a stronger effect on ribosomal subunit joining than does a comparable reduction of wild-type 60S levels conferred by A. We suggest that rpl33a-G76R alters 60S in a way that impedes ribosomal subunit joining and thereby allows 48S complexes to abort initiation at uORF4, resume scanning and initiate downstream at GCN4. Because overexpressing tRNA_i^Met suppresses the Gcd^- phenotype of rpl33a-G76R cells, dissociation of tRNA_i^Met from the 40S subunit may be responsible for abortive initiation at uORF4 in this mutant. We further demonstrate that rpl33a-G76R impairs efficient processing of 35S and 27S pre-rRNAs and reduces accumulation of all four mature rRNAs, indicating an important role for L33 in biogenesis of both ribosomal subunits.

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