Abstract
Translation is a core cellular process carried out by a highly conserved macromolecular machine, the ribosome. There has been remarkable evolutionary adaptation of this machine through the addition of eukaryote-specific ribosomal proteins whose individual effects on ribosome function are largely unknown. Here we show that eukaryote-specific Asc1/RACK1 is required for efficient translation of mRNAs with short open reading frames that show greater than average translational efficiency in diverse eukaryotes. ASC1 mutants in S. cerevisiae display compromised translation of specific functional groups, including cytoplasmic and mitochondrial ribosomal proteins, and display cellular phenotypes consistent with their gene-specific translation defects. Asc1-sensitive mRNAs are preferentially associated with the translational 'closed loop' complex comprised of eIF4E, eIF4G, and Pab1, and depletion of eIF4G mimics the translational defects of ASC1 mutants. Together our results reveal a role for Asc1/RACK1 in a length-dependent initiation mechanism optimized for efficient translation of genes with important housekeeping functions.
Highlights
Ribosomes are universal protein-synthesizing machines that are highly conserved in their structure and function throughout all kingdoms of life
Translation initiation in eukaryotes requires at least 12 initiation factors and proceeds by a complex series of steps beginning with recognition of the mRNA 50 cap structure, followed by unwinding of mRNA secondary structure, recruitment of the small (40S) ribosomal subunit, scanning, recognition of the initiation codon, and joining of the large (60S) ribosomal subunit to form a functional ribosome (Aitken and Lorsch, 2012)
We show that Asc1 is required for the efficient translation of short mRNAs, including those encoding cytoplasmic and mitochondrial ribosomal proteins
Summary
Ribosomes are universal protein-synthesizing machines that are highly conserved in their structure and function throughout all kingdoms of life. Eukaryotic ribosomes contain 13 domain-specific proteins that may play roles in translation initiation, which is both more complicated and more highly regulated in eukaryotes than in prokaryotes (Ban et al, 2014; Sonenberg and Hinnebusch, 2009). Recruitment of prokaryotic ribosomes to mRNAs requires only three initiation factors, IF1, 2, and 3, and relies on base-pairing between the RNA of the small ribosomal subunit and the anti-Shine-Delgarno sequence of the mRNA (Boelens and Gualerzi, 2002).
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