5'-end surveillance by Xrn2 acts as a shared mechanism for mammalian pre-rRNA maturation and decay

Nucleic Acids Res. 2011 Mar;39(5):1811-22. doi: 10.1093/nar/gkq1050. Epub 2010 Oct 29.

Abstract

Ribosome biogenesis requires multiple nuclease activities to process pre-rRNA transcripts into mature rRNA species and eliminate defective products of transcription and processing. We find that in mammalian cells, the 5' exonuclease Xrn2 plays a major role in both maturation of rRNA and degradation of a variety of discarded pre-rRNA species. Precursors of 5.8S and 28S rRNAs containing 5' extensions accumulate in mouse cells after siRNA-mediated knockdown of Xrn2, indicating similarity in the 5'-end maturation mechanisms between mammals and yeast. Strikingly, degradation of many aberrant pre-rRNA species, attributed mainly to 3' exonucleases in yeast studies, occurs 5' to 3' in mammalian cells and is mediated by Xrn2. Furthermore, depletion of Xrn2 reveals pre-rRNAs derived by cleavage events that deviate from the main processing pathway. We propose that probing of pre-rRNA maturation intermediates by exonucleases serves the dual function of generating mature rRNAs and suppressing suboptimal processing paths during ribosome assembly.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Exoribonucleases / antagonists & inhibitors
  • Exoribonucleases / physiology*
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins / physiology
  • RNA Precursors / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA Stability
  • RNA, Ribosomal / metabolism*

Substances

  • Nuclear Proteins
  • RNA Precursors
  • RNA, Ribosomal
  • Exoribonucleases
  • Xrn2 protein, mouse