ArticleNucleic acids research2024
Alternative translation initiation by ribosomal leaky scanning produces multiple isoforms of the Pif1 helicase.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- 5' UTR length shapes alternative N-terminal protein isoforms across cancers and in rare disease.EMBO reports · 2026Article
- 5' UTR length regulates alternative N-terminal protein isoform production in health and disease.bioRxiv : the preprint server for biology · 2026Article
- Alternative start codon selection shapes mitochondrial function and rare human diseases.Molecular cell · 2025Article
- Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.bioRxiv : the preprint server for biology · 2024Article
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2 authors.
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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-deficient (pif1-m2) alleles, with mutations in the first or second AUG codon, respectively. We have taken advantage of this refined model to develop improved versions of these alleles, which will serve as valuable tools to elucidate novel functions of this helicase and to disambiguate previously described genetic interactions of PIF1 in the context of nuclear and mitochondrial genome stability.
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