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.
Related
- Hepatocyte nuclear factor-1β recruits the nucleosome remodeling and deacetylase complex to activate gene transcription
- Cryo-EM structure of bixafen-bound S. cerevisiae complex II unravels SDHI specificity against pathogenic fungi
- Blueberry phytochemicals modulate the gut-vascular axis through microbiome-metabolome interaction.
- MDS-causing mutations of ZRSR2 impair minor intron splicing by reducing its interaction with SF3B complex
- Interaction of Discoidin Domain Receptor 1 with a 14-3-3-Beclin-1-Akt1 Complex Modulates Glioblastoma Therapy Sensitivity
BibTeX
@misc{sene2026pho92,
title = {{Pho92 direct interaction with Not1 recruits the CCR4-NOT complex to m6A containing mRNAs to modulate meiosis in S. cerevisiae}},
author = {L. Sene and D. Hazra and J. Scutenaire and N. Morellet and N. Ulryck and M. Matelot and H. Bounoua and M. Raji and S. Afensiss and B. Morlet and C. van Heijenoort and B. Seraphin and M. Graille},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.762167},
url = {https://www.biorxiv.org/content/10.64898/2026.10.27.762167v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Pho92 direct interaction with Not1 recruits the CCR4-NOT complex to m6A containing mRNAs to modulate meiosis in S. cerevisiae
AU - L. Sene
AU - D. Hazra
AU - J. Scutenaire
AU - N. Morellet
AU - N. Ulryck
AU - M. Matelot
AU - H. Bounoua
AU - M. Raji
AU - S. Afensiss
AU - B. Morlet
AU - C. van Heijenoort
AU - B. Seraphin
AU - M. Graille
PY - 2026
DA - 2026/10/27
PB - bioRxiv
DO - 10.64898/2026.10.27.762167
UR - https://www.biorxiv.org/content/10.64898/2026.10.27.762167v1
AB - 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.
ER -