Rio1 downregulates centromeric RNA levels to promote the timely assembly of structurally fit kinetochores

ABSTRACT: Kinetochores assemble on centromeres via histone H3 variant CENP-A and low levels of noncoding centromere transcripts (cenRNAs). The latter are ensured by transcription factor Cbf1 (S. cerevisiae), centromere-binding protein CENP-B (humans), and the local histone code downregulating RNA polymerase II (RNAPII) activity. CenRNAs levels are further adjusted by the nuclear exosome. Using S. cerevisiae, we now add kinase Rio1 to this scheme. Yeast cenRNAs are produced mostly from the periCEN regions as short (median lengths of 231nt) or long (4,458nt) transcripts, in a 1:1 ratio. Rio1 limits their production by reducing RNAPII access and transcription activity, and promotes their turnover by the 5’-3’exoribonuclease Rat1. Rio1 similarly curtails the concentrations of noncoding pericenRNAs, which nevertheless exist at a magnitude higher level than the cenRNAs. Similar to yeast, human cells depleted of orthologue RioK1 exhibit cenRNA buildup, kinetochore malformation, and chromosomal instability, suggesting that CEN regulation by Rio1/RioK1 is evolutionary conserved.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

TISSUE(S): Cell Culture

SUBMITTER: Romina Belli  

LAB HEAD: Peter Arthur Irene De Wulf

PROVIDER: PXD038337 | Pride | 2023-07-20

REPOSITORIES: Pride