The box C/D snoRNP assembly factor Bcd1 interacts with the histone chaperone Rtt106 and controls its transcription dependent activity

Benoît Bragantini,Sarah Cianférani,Édouard Bertrand ,Jean‐Marc Strub ,Decebal Tiotiu,Maxime Bourguet,Guillaume Terral,Arnaud Paul,Séverine Massenet,Hélène Marty,Benjamin Rothé,Xavier Manival,Steve Hessmann,Stéphane Labialle,Marc Quinternet,Laurence Decourty,Marie-Eve Chagot,Christophe Charron,Cosmin Saveanu,Bruno Charpentier

doi:10.1038/s41467-021-22077-4

Abstract

Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd1 protein. We present genetic interactions between the Rsa1p-encoding gene and genes involved in chromatin organization including RTT106 that codes for the H3-H4 histone chaperone Rtt106p controlling H3K56ac deposition. We show that Bcd1p binds Rtt106p and controls its transcription-dependent recruitment by reducing its association with RNA polymerase II, modulating H3K56ac levels at gene body. We reveal the 3D structures of the free and Rtt106p-bound forms of Bcd1p using nuclear magnetic resonance and X-ray crystallography. The interaction is also studied by a combination of biophysical and proteomic techniques. Bcd1p interacts with a region that is distinct from the interaction interface between the histone chaperone and histone H3. Our results are evidence for a protein interaction interface for Rtt106p that controls its transcription-associated activity.

Highlights

Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd[1] protein
We focused on the Rtt[106] protein as it is linked to several fundamental functions such as DNA replication, stability, and transcription, but not yet to snoRNP biogenesis and function, except for the observation based on modified chromatin immunopurification[38] suggesting that it can associate with complexes containing Rvb1/2 proteins in the vicinity of chromatin
Here, we report on a link between the machinery involved in box C/D snoRNP assembly and the machinery for chromatin assembly and remodeling

Summary

Introduction

Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd[1] protein. We present genetic interactions between the Rsa1p-encoding gene and genes involved in chromatin organization including RTT106 that codes for the H3-H4 histone chaperone Rtt106p controlling H3K56ac deposition. We show that Bcd1p binds Rtt106p and controls its transcription-dependent recruitment by reducing its association with RNA polymerase II, modulating H3K56ac levels at gene body. Our results are evidence for a protein interaction interface for Rtt106p that controls its transcription-associated activity. These particles primarily catalyze post-transcriptional modifications in ribosomal RNAs2 (rRNAs) In these reactions, the snoRNA functions as a guide by base-pairing with a target sequence and selecting the precise nucleotide that will be modified by the catalytic activity of the snoRNP3. This process requires assembly machinery including the protein heterodimer Rsa1:Hit[17] and the

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Results

Conclusion