Alternative translation initiation by ribosomal leaky scanning produces multiple isoforms of the Pif1 helicase.

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

SUBMITTER: Lama-Diaz T 

PROVIDER: S-EPMC11229318 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature