Pbp1 associates with Puf3 and promotes translation of its target mRNAs involved in mitochondrial biogenesis

Pbp1 (polyA-binding protein - binding protein 1) is a stress granule marker and polyglutamine expansions in its mammalian ortholog ataxin-2 have been linked to neurodegenerative conditions. Pbp1 was recently shown to form intracellular assemblies that function in the negative regulation of TORC1 signaling under respiratory conditions. Furthermore, it was observed that loss of Pbp1 leads to mitochondrial dysfunction. Here, we show that loss of Pbp1 leads to a specific decrease in mitochondrial proteins whose encoding mRNAs are targets of the RNA-binding protein Puf3, suggesting a functional relationship between Pbp1 and Puf3. We found that Pbp1 stabilizes and promotes the translation of Puf3-target mRNAs in respiratory conditions, such as those involved in the assembly of cytochrome c oxidase. We further show that Pbp1 and Puf3 associate through their respective low complexity domains, which is required for target mRNA stabilization and translation. Our findings reveal a key role for Pbp1-containing assemblies in enabling the translation of mRNAs critical for mitochondrial biogenesis and respiration under metabolically challenging conditions. They may further explain prior associations of Pbp1/ataxin-2 with stress granule biology and RNA metabolism. Two biological replicates of wild type or ∆pbp1 cells grown in YPD media or switched from YPD to YPL media and grown for an additional 3 hrs were collected for RNA-seq.