The Implication of mRNA Degradation Disorders on Human DISease: Focus on DIS3 and DIS3-Like Enzymes

Margarida Saramago, Paulo J. da Costa, Sandra C. Viegas, Cecí­lia M. Arraiano

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

7 Citations (Scopus)

Abstract

RNA degradation is considered a critical posttranscriptional regulatory checkpoint, maintaining the correct functioning of organisms. When a specific RNA transcript is no longer required in the cell, it is signaled for degradation through a number of highly regulated steps. Ribonucleases (or simply RNases) are key enzymes involved in the control of RNA stability. These enzymes can perform the RNA degradation alone or cooperate with other proteins in RNA degradation complexes. Important findings over the last years have shed light into eukaryotic RNA degradation by members of the RNase II/RNB family of enzymes. DIS3 enzyme belongs to this family and represents one of the catalytic subunits of the multiprotein complex exosome. This RNase has a diverse range of functions, mainly within nuclear RNA metabolism. Humans encode two other DIS3-like enzymes: DIS3L (DIS3L1) and DIS3L2. DIS3L1 also acts in association with the exosome but is strictly cytoplasmic. In contrast, DIS3L2 acts independently of the exosome and shows a distinctive preference for uridylated RNAs. These enzymes have been shown to be involved in important cellular processes, such as mitotic control, and associated with human disorders like cancer. This review shows how the impairment of function of each of these enzymes is implicated in human disease.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages85-98
Number of pages14
DOIs
Publication statusPublished - 1 Jan 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1157
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Cancer
  • DIS3
  • DIS3L1
  • DIS3L2
  • Exoribonuclease
  • Exosome
  • Polyadenylation
  • RNA degradation
  • RNase
  • Uridylation

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