Recruitment of factors linking transcription and processing of pre-rRNA to NOR chromatin is UBF-dependent and occurs independent of transcription in human cells

Genes Dev. 2007 Aug 15;21(16):2041-54. doi: 10.1101/gad.436707.

Abstract

Efficient ribosome biogenesis requires coordination of a highly complex series of events. Early events include pre-RNA transcription, processing, and modification. Analysis in yeast has demonstrated that t-UTPs, components of the U3 snoRNA-containing pre-rRNA processing complex, are required for efficient transcription of ribosomal genes (rDNA) by RNA polymerase I (pol I). Here, we characterize human t-UTPs and establish that their ability to link transcription and pre-rRNA processing is evolutionarily conserved. The pol I transcription factor UBF binds extensively across rDNA throughout the cell cycle, resulting in a specialized form of chromatin that is the hallmark of active nucleolar organizer regions (NORs). Transcriptionally silent pseudo-NORs are ectopic, chromosomally integrated, artificial arrays that mimic this specialized chromatin structure. Pseudo-NORs sequester t-UTPs and factors linking transcription with pre-rRNA modification (Nopp140 and Treacle). Recruitment is independent of transcription, the underlying DNA sequence, and location within the nucleolus. Previously, we have demonstrated that pseudo-NORs sequester every component of the pol I transcription machinery. Taken together, these results highlight the importance of the specialized chromatin structure at active NORs in coordinating early events in ribosome biogenesis and nucleolar formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Cycle
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA, Ribosomal / genetics
  • DNA, Ribosomal / metabolism
  • HeLa Cells
  • Humans
  • Multiprotein Complexes
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleolus Organizer Region / genetics
  • Nucleolus Organizer Region / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Pol1 Transcription Initiation Complex Proteins / metabolism*
  • RNA Polymerase I / genetics
  • RNA Polymerase I / metabolism
  • RNA Precursors / genetics
  • RNA Precursors / metabolism*
  • RNA Processing, Post-Transcriptional
  • RNA, Small Interfering / genetics
  • Ribonucleoproteins, Small Nucleolar / genetics
  • Ribonucleoproteins, Small Nucleolar / metabolism
  • Transcription, Genetic

Substances

  • Chromatin
  • DNA, Ribosomal
  • Multiprotein Complexes
  • NOLC1 protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • Pol1 Transcription Initiation Complex Proteins
  • RNA Precursors
  • RNA, Small Interfering
  • Ribonucleoproteins, Small Nucleolar
  • TCOF1 protein, human
  • ribonucleoprotein, U3 small nucleolar
  • transcription factor UBF
  • RNA Polymerase I