Exonuclease requirements for mammalian ribosomal RNA biogenesis and surveillance

Nat Struct Mol Biol. 2019 Jun;26(6):490-500. doi: 10.1038/s41594-019-0234-x. Epub 2019 Jun 3.

Abstract

Ribosomal RNA (rRNA) biogenesis is a multistep process requiring several nuclear and cytoplasmic exonucleases. The exact processing steps for mammalian 5.8S rRNA remain obscure. Here, using loss-of-function approaches in mouse embryonic stem cells (mESCs) and deep sequencing of rRNA intermediates, we investigate the requirements of exonucleases known to be involved in 5.8S maturation at nucleotide resolution and explore the role of the Perlman syndrome-associated 3'-5' exonuclease Dis3l2 in rRNA processing. We uncover a novel cytoplasmic intermediate that we name '7SB' rRNA that is generated through sequential processing by distinct exosome complexes. 7SB rRNA can be oligoadenylated by an unknown enzyme and/or oligouridylated by TUT4/7 and subsequently processed by Dis3l2 and Eri1. Moreover, exosome depletion triggers Dis3l2-mediated decay (DMD) as a surveillance pathway for rRNAs. Our data identify previously unknown 5.8S rRNA processing steps and provide nucleotide-level insight into the exonuclease requirements for mammalian rRNA processing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Exoribonucleases / metabolism*
  • Fetal Macrosomia / metabolism
  • Mice
  • Mouse Embryonic Stem Cells / metabolism
  • RNA Transport
  • RNA, Ribosomal, 5.8S / metabolism*
  • Ribosomes / metabolism
  • Uridine / metabolism
  • Wilms Tumor / metabolism

Substances

  • DNA-Binding Proteins
  • RNA, Ribosomal, 5.8S
  • ZCCHC11 protein, mouse
  • Dis3l2 protein, mouse
  • Eri1 protein, mouse
  • Exoribonucleases
  • Uridine

Supplementary concepts

  • Nephroblastomatosis, fetal ascites, macrosomia and Wilms tumor