Pbp1 stabilizes and promotes the translation of Puf3-target mRNAs involved in mitochondrial biogenesis

Abstract

Pbp1 (poly(A)-binding protein - binding protein 1) is a cytoplasmic stress granule marker that is capable of forming condensates that function in the negative regulation of TORC1 signaling under respiratory conditions. How mutations in its mammalian ortholog ataxin-2 are linked to neurodegenerative conditions remains unclear. Here, we show that loss of Pbp1 leads to decreases in amounts of mitochondrial proteins whose encoding mRNAs are targets of Puf3, a member of the PUF (Pumilio and FBF) family of RNA-binding proteins. 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 interact through their respective low complexity domains, which is required for Puf3-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. They may further begin to explain prior associations of Pbp1/ataxin-2 with RNA, stress granule biology, mitochondrial function, and neuronal health.