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Nucleic Acids Res. 2016 Oct 14;44(18):8826-8841. Epub 2016 Aug 31.

Tma108, a putative M1 aminopeptidase, is a specific nascent chain-associated protein in Saccharomyces cerevisiae.

Author information

1
Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie computationnelle et quantitative - Institut de Biologie Paris Seine (LCQB - IBPS), 75005 Paris, France.
2
Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
3
Proteomics facility, Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
4
Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie computationnelle et quantitative - Institut de Biologie Paris Seine (LCQB - IBPS), 75005 Paris, France mathilde.garcia@upmc.fr.

Abstract

The discovery of novel specific ribosome-associated factors challenges the assumption that translation relies on standardized molecular machinery. In this work, we demonstrate that Tma108, an uncharacterized translation machinery-associated factor in yeast, defines a subpopulation of cellular ribosomes specifically involved in the translation of less than 200 mRNAs encoding proteins with ATP or Zinc binding domains. Using ribonucleoparticle dissociation experiments we established that Tma108 directly interacts with the nascent protein chain. Additionally, we have shown that translation of the first 35 amino acids of Asn1, one of the Tma108 targets, is necessary and sufficient to recruit Tma108, suggesting that it is loaded early during translation. Comparative genomic analyses, molecular modeling and directed mutagenesis point to Tma108 as an original M1 metallopeptidase, which uses its putative catalytic peptide-binding pocket to bind the N-terminus of its targets. The involvement of Tma108 in co-translational regulation is attested by a drastic change in the subcellular localization of ATP2 mRNA upon Tma108 inactivation. Tma108 is a unique example of a nascent chain-associated factor with high selectivity and its study illustrates the existence of other specific translation-associated factors besides RNA binding proteins.

PMID:
27580715
PMCID:
PMC5062994
DOI:
10.1093/nar/gkw732
[Indexed for MEDLINE]
Free PMC Article

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