The ribosomal protein Asc1/RACK1 is required for efficient translation of short mRNAs.
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.
Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
Mary K
0000-0002-4947-6048
MK
Thompson
Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
Maria F
MF
Rojas-Duran
Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
Paritosh
0000-0002-4893-8167
P
Gangaramani
Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
Wendy V
0000-0003-2807-9657
WV
Gilbert
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
C111825:ASC1 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D019204:GTP-Binding Proteins
Asc1; RACK1; S. cerevisiae; biochemistry; ribosome; translation