July 8th, 2024 (2/2)

Today is a special day for the lab. The current issue of Nucleic Acids Research features two papers from the group reflecting the PhD projects of Tomás Lama Díaz and Raquel Carreira Rodríguez.

In Alternative translation initiation by ribosomal leaky scanning produces multiple isoforms of the Pif1 helicase, Tomás wrestled with the complex alternative translation initiation mechanism that enables the generation of mitochondrial and nuclear isoforms of this conserved helicase from the same mRNA. He demonstrated that ribosomal leaky scanning produces not only these, but also novel, previously uncharacterized Pif1 isoforms, with a contribution of both in-frame, downstream AUGs as well as near-cognate start codons. This provides an explanation for long-observed,  suboptimal behaviour of the widely employed mitochondrial- (pif1-m1) and nuclear-deficient (pif1-m2) alleles. Importantly, we have taken advantage of this refined model of PIF1 mRNA translation to develop improved mitochondrial- and nuclear-null pif1 mutants, 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.