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

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  • Mengjun Wu, University of Copenhagen
  • ,
  • Evdoxia Karadoulama, University of Copenhagen
  • ,
  • Marta Lloret-Llinares, European Molecular Biology Laboratory
  • ,
  • Jerome Olivier Rouviere
  • Christian Skov Vaagensø, University of Copenhagen
  • ,
  • Martin Moravec
  • ,
  • Bingnan Li, Karolinska Institutet
  • ,
  • Jingwen Wang, Karolinska Institutet
  • ,
  • Guifen Wu
  • Maria Gockert
  • Vicent Pelechano, Karolinska Institutet
  • ,
  • Torben Heick Jensen
  • Albin Sandelin, University of Copenhagen

The ribonucleolytic exosome complex is central for nuclear RNA degradation, primarily targeting non-coding RNAs. Still, the nuclear exosome could have protein-coding (pc) gene-specific regulatory activities. By depleting an exosome core component, or components of exosome adaptor complexes, we identify ∼2900 transcription start sites (TSSs) from within pc genes that produce exosome-sensitive transcripts. At least 1000 of these overlap with annotated mRNA TSSs and a considerable portion of their transcripts share the annotated mRNA 3' end. We identify two types of pc-genes, both employing a single, annotated TSS across cells, but the first type primarily produces full-length, exosome-sensitive transcripts, whereas the second primarily produces prematurely terminated transcripts. Genes within the former type often belong to immediate early response transcription factors, while genes within the latter are likely transcribed as a consequence of their proximity to upstream TSSs on the opposite strand. Conversely, 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 transcripts are prematurely terminated. Our results display a complex landscape of sense transcription within pc-genes and imply a direct role for nuclear RNA turnover in the regulation of a subset of pc-genes.

Original languageEnglish
JournalNucleic Acids Research
Pages (from-to)8509-8528
Number of pages20
Publication statusPublished - Sep 2020

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