Pho92 direct interaction with Not1 recruits the CCR4-NOT complex to m6A containing mRNAs to modulate meiosis in S. cerevisiae

Abstract

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNAs. In S. cerevisiae, m6A is exclusively deposited during meiosis, where it plays an essential role in meiotic progression. In this context, the absence of Pho92, the sole known m6A-binding protein in budding yeast, leads to the abnormal persistence of m6A-containing mRNAs, ultimately resulting in delayed meiosis. Here, we investigate how m6A recognition by Pho92 regulates gene expression. Using complementary in vivo and in vitro approaches, we identify direct interactions between Pho92 and Not1, the scaffold subunit of the CCR4-NOT deadenylase complex. Structural analyses reveal that a short evolutionarily conserved motif in Pho92 adopts an -helical conformation that docks onto specific regions of Not1. Functionally, these interactions are required for efficient meiotic progression. Altogether, our findings demonstrate that Pho92 couples m6A recognition to the main deadenylase to shape the meiotic transcriptome. More broadly, our work provides mechanistic insights into how epitranscriptomic signals interface with the core mRNA decay machinery to regulate gene expression during cellular differentiation.