FUNDING Biotechnology and Biological Sciences Research Council (BBSRC) [BB/I020926/1 to I.S.]; BBSRC PhD studentship award [C103817D to I.S. and M.C.R.]; Scottish Universities Life Science Alliance PhD studentship award (to M.C.R. and I.S.]. Funding for open access charge: BBSRC. Conflict of interest statement. None declared.Peer reviewedPublisher PD

Ciandrini, Luca

Gorgoni, Barbara

McFarland, Matthew R.

Romano, M. Carmen

Stansfield, Ian

Nucleic Acids Research

English

PubMed

International audiencetRNA gene copy number is a primary determinant of tRNA abundance and therefore the rate at which each tRNA delivers amino acids to the ribosome during translation. Low-abundance tRNAs decode rare codons slowly, but it is unclear which genes might be subject to tRNA-mediated regulation of expression. Here, those mRNA targets were identified via global simulation of translation. In-silico mRNA translation rates were compared for each mRNA in both wild-type and a [Formula: see text] sup70-65 mutant, which exhibits a pseudohyphal growth phenotype and a 75% slower CAG codon translation rate. Of 4900 CAG-containing mRNAs, 300 showed significantly reduced in silico translation rates in a simulated tRNA mutant. Quantitative immunoassay confirmed that the reduced translation rates of sensitive mRNAs were [Formula: see text] concentration-dependent. Translation simulations showed that reduced [Formula: see text] concentrations triggered ribosome queues, which dissipated at reduced translation initiation rates. To validate this prediction experimentally, constitutive gcn2 kinase mutants were used to reduce in vivo translation initiation rates. This repaired the relative translational rate defect of target mRNAs in the sup70-65 background, and ameliorated sup70-65 pseudohyphal growth phenotypes. We thus validate global simulation of translation as a new tool to identify mRNA targets of tRNA-specific gene regulation

CIANDRINI, Luca

Mcfarland, Matthew r

Romano, M carmen

HAL Descartes

Identification of the mRNA targets of tRNA-specific regulation using genome-wide simulation of translation.

Research Archive

Identification of the mRNA targets of tRNA-specific regulation using genome-wide simulation of translation

Identification of the mRNA targets of tRNA-specific regulation using genome-wide simulation of translation

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