{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lama-Diaz T"],"funding":["Xunta de Galicia","Xunta de Galicia/FEDER ‘Una manera de hacer Europa’","Ministerio de Ciencia e Innovación","Centro Singular de Investigación de Galicia","CIMUS receives financial support from the Xunta de Galicia/FEDER","Xunta de Galicia/FEDER 'Una manera de hacer Europa'"],"pagination":["6928-6944"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11229318"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["52(12)"],"pubmed_abstract":["In budding yeast, the integrity of both the nuclear and mitochondrial genomes relies on dual-targeted isoforms of the conserved Pif1 helicase, generated by alternative translation initiation (ATI) of PIF1 mRNA from two consecutive AUG codons flanking a mitochondrial targeting signal. Here, we demonstrate that ribosomal leaky scanning is the specific ATI mechanism that produces not only these, but also novel, previously uncharacterized Pif1 isoforms. Both in-frame, downstream AUGs as well as near-cognate start codons contribute to the generation of these alternative isoforms. This has crucial implications for the rational design of genuine separation-of-function alleles and provides an explanation for the suboptimal behaviour of the widely employed mitochondrial- (pif1-m1) and nuclear-defic"],"journal":["Nucleic acids research"],"pubmed_title":["Alternative translation initiation by ribosomal leaky scanning produces multiple isoforms of the Pif1 helicase."],"pmcid":["PMC11229318"],"funding_grant_id":["PID2020-115472GB-I00","2019–2022","ED481A-2018/042","2019-2022","ED431G 2019/02","ED431C 2019/013"],"pubmed_authors":["Lama-Diaz T","Blanco MG"],"additional_accession":[]},"is_claimable":false,"name":"Alternative translation initiation by ribosomal leaky scanning produces multiple isoforms of the Pif1 helicase.","description":"In budding yeast, the integrity of both the nuclear and mitochondrial genomes relies on dual-targeted isoforms of the conserved Pif1 helicase, generated by alternative translation initiation (ATI) of PIF1 mRNA from two consecutive AUG codons flanking a mitochondrial targeting signal. Here, we demonstrate that ribosomal leaky scanning is the specific ATI mechanism that produces not only these, but also novel, previously uncharacterized Pif1 isoforms. Both in-frame, downstream AUGs as well as near-cognate start codons contribute to the generation of these alternative isoforms. This has crucial implications for the rational design of genuine separation-of-function alleles and provides an explanation for the suboptimal behaviour of the widely employed mitochondrial- (pif1-m1) and nuclear-defic","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2025-04-04T11:25:20.557Z","creation":"2025-04-04T11:25:20.557Z"},"accession":"S-EPMC11229318","cross_references":{"pubmed":["38783074"],"doi":["10.1093/nar/gkae400"]}}