PT  - JOURNAL ARTICLE
AU  - Sara Luzzi
AU  - Ugo Szachnowski
AU  - Sarah Greener
AU  - Camille Gautier
AU  - Kang Hoo Han
AU  - Jack Darke
AU  - Rossana Piccinno
AU  - Anne Lafon
AU  - B. Franklin Pugh
AU  - Antonin Morillon
AU  - Manolis Papamichos-Chronakis
TI  - The INO80 remodeler couples premature termination of mRNA synthesis with transcription elongation
AID  - 10.1101/2020.03.02.973685
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.02.973685
4099  - http://biorxiv.org/content/early/2020/03/04/2020.03.02.973685.short
4100  - http://biorxiv.org/content/early/2020/03/04/2020.03.02.973685.full
AB  - 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.