A long non-coding RNA is required for targeting centromeric protein A to the human centromere

Elife. 2014 Aug 12;3:e03254. doi: 10.7554/eLife.03254.

Abstract

The centromere is a specialized chromatin region marked by the histone H3 variant CENP-A. Although active centromeric transcription has been documented for over a decade, the role of centromeric transcription or transcripts has been elusive. Here, we report that centromeric α-satellite transcription is dependent on RNA Polymerase II and occurs at late mitosis into early G1, concurrent with the timing of new CENP-A assembly. Inhibition of RNA Polymerase II-dependent transcription abrogates the recruitment of CENP-A and its chaperone HJURP to native human centromeres. Biochemical characterization of CENP-A associated RNAs reveals a 1.3 kb molecule that originates from centromeres, which physically interacts with the soluble pre-assembly HJURP/CENP-A complex in vivo, and whose down-regulation leads to the loss of CENP-A and HJURP at centromeres. This study describes a novel function for human centromeric long non-coding RNAs in the recruitment of HJURP and CENP-A, implicating RNA-based chaperone targeting in histone variant assembly.

Keywords: CENP-A; centromeres; chromatin; epigenetics; histone variants; lncRNA.

Publication types

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

MeSH terms

  • Autoantigens / genetics*
  • Autoantigens / metabolism
  • Centromere / chemistry
  • Centromere / metabolism*
  • Centromere Protein A
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • HeLa Cells
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Mitosis
  • Protein Binding
  • Protein Transport
  • RNA Polymerase II / antagonists & inhibitors
  • RNA Polymerase II / genetics*
  • RNA Polymerase II / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transcription, Genetic

Substances

  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • HJURP protein, human
  • Histones
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • RNA Polymerase II