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The RNA exosome shapes the expression of key protein-coding genes

ABSTRACT: The ribonucleolytic exosome complex is central for nuclear RNA degradation, primarily targeting non-coding RNAs, while the majority of mRNAs are protected through their 3’ polyadenylation and nuclear export. Still, the nuclear exosome could have protein-coding (pc) gene-specific regulatory activities. By depleting an exosome core component, or key components of nucleoplasmic exosome adaptor complexes, we identify a number of transcription start sites (TSSs) from within pc genes that produce exosome-sensitive transcripts and two classes of pc-genes, which both employ a single, annotated TSS across cells and tissues, but the former class primarily produces full-length, exosome-sensitive transcripts, whereas the latter primarily produces prematurely terminated transcripts. Genes within the former class often belong to immediate early response transcription factors, while genes within the latter are likely transcribed as a consequence of their proximity to strong upstream TSSs on the opposite strand. We also show that when genes have multiple active TSSs, alternative TSSs that produce exosome sensitive transcripts typically do not contribute substantially to overall gene expression, and most such exosome sensitive transcripts are prematurely terminated. Our results display a complex landscape of sense transcription within pc-gene regions and imply a direct role for nuclear RNA turnover in the expression regulation of a subset of pc- genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147655 | GEO | 2020/06/29

REPOSITORIES: GEO

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An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression

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