Abstract
The genome is pervasively transcribed across various species, yielding numerous non-coding RNAs. As a counterbalance for pervasive transcription, various organisms have a nuclear RNA exosome complex, whose structure is well conserved between yeast and mammalian cells. The RNA exosome not only regulates the processing of stable RNA species, such as rRNAs, tRNAs, small nucleolar RNAs, and small nuclear RNAs, but also plays a central role in RNA surveillance by degrading many unstable RNAs and misprocessed pre-mRNAs. In addition, associated cofactors of RNA exosome direct the exosome to distinct classes of RNA substrates, suggesting divergent and/or multi-layer control of RNA quality in the cell. While the RNA exosome is essential for cell viability and influences various cellular processes, mutations and alterations in the RNA exosome components are linked to the collection of rare diseases and various diseases including cancer, respectively. The present review summarizes the relationships between pervasive transcription and RNA exosome, including evolutionary crosstalk, mechanisms of RNA exosome-mediated RNA surveillance, and physiopathological effects of perturbation of RNA exosome.
Highlights
The present review summarizes the relationships between pervasive transcription and RNA exosome, including evolutionary crosstalk, mechanisms of RNA exosome-mediated RNA surveillance, and physiopathological effects of perturbation of RNA exosome
Various phenotypes observed upon perturbation of the RNA exosome and cofactors may be viewed as functions of the RNA exosome, independent of the counterbalance system for pervasive transcription
Given that various RNA molecules targeted by the RNA exosome play important roles in intracellular liquid-liquid phase separation (LLPS), the biology of biomolecular condensate and LLPS may be intimately associated with the functions of the RNA exosome [121,122]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Transcription forms an initial foundation of the gene expression programs; eukaryotic genomes, including those of yeasts, are pervasively transcribed beyond the canonical protein-coding genes and representative non-coding RNA genes, such as rRNAs, yielding numerous RNA species such as long non-coding RNAs (lncRNAs), upstream antisense RNAs (uaRNAs, known as promoter upstream transcripts (PROMPTs) in mammals or cryptic unstable transcripts (CUTs) in yeasts), transcription start site (TSS)-associated RNAs (tssRNAs), and enhancer RNAs (eRNAs) [1,2]. These RNA species are unstable and subject to rapid degradation by the RNA exosome complex, a counterbalance system for pervasive transcription. Studied in various species including yeasts and flies, this review mainly focuses on the findings in mammalian cells
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