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The INO80 remodeler couples premature termination of mRNA synthesis with transcription elongation

Lookup NU author(s): Dr Sara LuzziORCiD, Sarah Marshall, Dr Manolis Papamichos Chronakis


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RNA quality control and timely termination of aberrant transcription are critical for functional gene expression. Here, we report that in Saccharomyces cerevisiae premature transcription termination of mRNAs is coordinated with the transcriptional elongation process and regulated by the evolutionarily conserved ATP-dependent chromatin remodeling complex INO80. Loss of INO80 sensitizes cells to the transcriptional elongation stress drug 6-azauracil and leads to enhanced pausing of elongating RNA Polymerase II across the genome. Transcriptional pausing positively correlates with premature termination of mRNA transcription and is pronounced proximally to promoters at sites of enhanced histone H3 binding to DNA. Cells with deficient INO80 complex accumulate short, unproductive mRNA transcripts on chromatin and are defective in transcription termination mediated by the Nrd1-Nab3-Sen1 (NNS) complex. We find that loss of INO80 compromises the interaction of the RNA surveillance factor Nab2 with short promoter-proximal mRNA transcripts. INO80 promotes co-transcriptional recruitment of Nab2 to chromatin by enabling its interaction with the histone variant H2A.Z. Finally, inactivation of the histone deacetylase complex Rpd3S/Rco1 reduces promoter-proximal pausing and enhances productive transcription through an NNS-dependent termination site when INO80 is compromised. Our work suggests that, by regulation of H2A.Z-containing nucleosomes, INO80 orchestrates a mechanism for premature transcription termination, linking RNA quality control to the transcriptional process.

Publication metadata

Author(s): Luzzi S, Szachnowski U, Greener S, Gautier C, Han KH, Darke J, Piccinno R, Lafon A, Pugh BF, Morillon A, Papamichos-Chronakis M

Publication type: Article

Publication status: Unpublished

Journal: bioRxiv

Year: 2020

Publisher: Cold Spring Harbor Laboratory


DOI: 10.1101/2020.03.02.973685


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