title: mTOR-sensitive translation: Cleared fog reveals more trees.
abstract: Translation is fundamental for many biologic processes as it enables cells to rapidly respond to stimuli without requiring de novo mRNA synthesis. The mammalian/mechanistic target of rapamycin (mTOR) is a key regulator of translation. Although mTOR affects global protein synthesis, translation of a subset of mRNAs appears to be exceptionally sensitive to changes in mTOR activity. Recent efforts to catalog these mTOR-sensitive mRNAs resulted in conflicting results. Whereas ribosome-profiling almost exclusively identified 5'-terminal oligopyrimidine (TOP) mRNAs as mTOR-sensitive, polysome-profiling suggested that mTOR also regulates translation of non-TOP mRNAs. This inconsistency was explained by analytical and technical biases limiting the efficiency of ribosome-profiling in detecting mRNAs showing differential translation. Moreover, genome-wide characterization of 5'UTRs of non-TOP mTOR-sensitive mRNAs revealed 2 subsets of transcripts which differ in their requirement for translation initiation factors and biologic functions. We summarize these recent advances and their impact on the understanding of mTOR-sensitive translation.
authors.affiliation: a Department of Oncology-Pathology , Science for Life Laboratory, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Laia
authors.initials: L
authors.lastname: Masvidal
authors.affiliation: b Lady Davis Institute, SMBD Jewish General Hospital , Montreal , Canada.|c Gerald-Bronfman Department of Oncology, Departments of Experimental Medicine , and Biochemistry McGill University , Montreal , Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Hulea
authors.affiliation: d Cancer Program , Biomedicine Discovery Institute and Department of Anatomy & Developmental Biology, Monash University , Victoria , Australia.|e Prostate Cancer Translational Research Laboratory, Peter MacCallum Cancer Centre , Melbourne , Victoria , Australia.
authors.forename: Luc
authors.identifier: 0000-0002-1893-9812
authors.initials: L
authors.lastname: Furic
authors.affiliation: b Lady Davis Institute, SMBD Jewish General Hospital , Montreal , Canada.|c Gerald-Bronfman Department of Oncology, Departments of Experimental Medicine , and Biochemistry McGill University , Montreal , Canada.
authors.forename: Ivan
authors.initials: I
authors.lastname: Topisirovic
authors.affiliation: a Department of Oncology-Pathology , Science for Life Laboratory, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Larsson
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases
keywords: UTR; eIFs; mRNA translation; mTOR; nanoCAGE; polysome profiling; ribosome profiling