SLERT Regulates DDX21 Rings Associated with Pol I Transcription

Cell. 2017 May 4;169(4):664-678.e16. doi: 10.1016/j.cell.2017.04.011.

Abstract

Dysregulated rRNA synthesis by RNA polymerase I (Pol I) is associated with uncontrolled cell proliferation. Here, we report a box H/ACA small nucleolar RNA (snoRNA)-ended long noncoding RNA (lncRNA) that enhances pre-rRNA transcription (SLERT). SLERT requires box H/ACA snoRNAs at both ends for its biogenesis and translocation to the nucleolus. Deletion of SLERT impairs pre-rRNA transcription and rRNA production, leading to decreased tumorigenesis. Mechanistically, SLERT interacts with DEAD-box RNA helicase DDX21 via a 143-nt non-snoRNA sequence. Super-resolution images reveal that DDX21 forms ring-shaped structures surrounding multiple Pol I complexes and suppresses pre-rRNA transcription. Binding by SLERT allosterically alters individual DDX21 molecules, loosens the DDX21 ring, and evicts DDX21 suppression on Pol I transcription. Together, our results reveal an important control of ribosome biogenesis by SLERT lncRNA and its regulatory role in DDX21 ring-shaped arrangements acting on Pol I complexes.

Keywords: DDX21; RNA polymerase I; SIM; SLERT; nucleolus; sno-lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Site
  • Animals
  • Carcinogenesis
  • Cell Line
  • Cell Line, Tumor
  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / metabolism*
  • Female
  • Gene Knockout Techniques
  • Humans
  • Mice
  • Mice, Nude
  • RNA Polymerase I / metabolism*
  • RNA Precursors / genetics*
  • RNA Precursors / metabolism
  • RNA, Long Noncoding / metabolism*
  • Transcription, Genetic

Substances

  • RNA Precursors
  • RNA, Long Noncoding
  • RNA Polymerase I
  • DDX21 protein, human
  • DEAD-box RNA Helicases