INO80 remodeler Links mRNA Quality Control To Transcriptional Regulation

Eukaryotic mRNAs undergo premature transcriptional termination and degradation to prevent aberrant expression of protein coding genes. mRNAs are subjected to co-transcriptional RNA surveillance and non-canonical transcriptional termination similar to non-coding RNAs. The Nrd1-Nab3-Sen1 (NNS) RNA binding complex and the nuclear exosome complex containing the 3’-5’ RNA exonuclease Rrp6 contribute to mRNA quality control, resulting in attenuation of transcription of protein coding genes. mRNA transcriptional attenuation is particularly pronounced during the early steps of transcriptional elongation by RNA Polymerase II. However, the mechanisms regulating premature mRNA termination remain poorly understood. Moreover, the extent to which transcriptional attenuation contributes to the production of functional mRNAs is unclear. Here we show that, in yeast, the evolutionary conserved ATP-dependent chromatin remodelling complex INO80 promotes the removal of aberrant native mRNA transcripts from chromatin to enable transcription elongation. Loss of INO80 leads to genome-wide accumulation of early terminated, nascent mRNAs at DNA contact sites for the histone H3 N-terminal tail proximally to promoters, abrogating productive transcription. INO80 interacts with Nrd1 and promotes RNA decay by facilitating non-canonical transcription termination. Retention of native mRNAs at promoter proximal sites is regulated by the Rpd3S Histone Deacetylation complex. Chromatin relaxation by disruption of Rpd3S at a site of non-canonical transcriptional termination rescues the defect in productive transcription of functional mRNAs caused by disruption of INO80. Our work reveals how chromatin organisation controls transcriptional attenuation to regulate productive gene expression.