{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Meurs R"],"funding":["Swiss National Science Foundation"],"pagination":["854-876"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11790910"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(3)"],"pubmed_abstract":["Ribosomes scanning from the mRNA 5' cap to the start codon may initiate at upstream open reading frames (uORFs), decreasing protein biosynthesis. Termination at a uORF can lead to re-initiation, where 40S subunits resume scanning and initiate another translation event downstream. The noncanonical translation factors MCTS1-DENR participate in re-initiation at specific uORFs, but knowledge of other trans-acting factors or uORF features influencing re-initiation is limited. Here, we establish a cell-free re-initiation assay using HeLa lysates to address this question. Comparing in vivo and in vitro re-initiation on uORF-containing reporters, we validate MCTS1-DENR-dependent re-initiation in vitro. Using this system and ribosome profiling in cells, we found that knockdown of the MCTS1-DENR hom"],"journal":["The EMBO journal"],"pubmed_title":["MCTS2 and distinct eIF2D roles in uORF-dependent translation regulation revealed by in vitro re-initiation assays."],"pmcid":["PMC11790910"],"funding_grant_id":["212423","205601"],"pubmed_authors":["Ban N","De Matos M","Teleman AA","Guex N","Weber T","Gatfield D","Bothe A","Meurs R"],"additional_accession":[]},"is_claimable":false,"name":"MCTS2 and distinct eIF2D roles in uORF-dependent translation regulation revealed by in vitro re-initiation assays.","description":"Ribosomes scanning from the mRNA 5' cap to the start codon may initiate at upstream open reading frames (uORFs), decreasing protein biosynthesis. Termination at a uORF can lead to re-initiation, where 40S subunits resume scanning and initiate another translation event downstream. The noncanonical translation factors MCTS1-DENR participate in re-initiation at specific uORFs, but knowledge of other trans-acting factors or uORF features influencing re-initiation is limited. Here, we establish a cell-free re-initiation assay using HeLa lysates to address this question. Comparing in vivo and in vitro re-initiation on uORF-containing reporters, we validate MCTS1-DENR-dependent re-initiation in vitro. Using this system and ribosome profiling in cells, we found that knockdown of the MCTS1-DENR hom","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-01T10:37:36.161Z","creation":"2025-04-04T01:02:30.307Z"},"accession":"S-EPMC11790910","cross_references":{"pubmed":["39748120"],"doi":["10.1038/s44318-024-00347-3"]}}