The A-repeat links ASF/SF2-dependent Xist RNA processing with random choice during X inactivation

Nat Struct Mol Biol. 2010 Aug;17(8):948-54. doi: 10.1038/nsmb.1877. Epub 2010 Jul 25.

Abstract

One X chromosome, selected at random, is silenced in each female mammalian cell. Xist encodes a noncoding RNA that influences the probability that the cis-linked X chromosome will be silenced. We found that the A-repeat, a highly conserved element within Xist, is required for the accumulation of spliced Xist RNA. In addition, the A-repeat is necessary for X-inactivation to occur randomly. In combination, our data suggest that normal Xist RNA processing is important in the regulation of random X-inactivation. We propose that modulation of Xist RNA processing may be part of the stochastic process that determines which X chromosome will be inactivated.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Base Sequence
  • Chromosomes, Mammalian / metabolism
  • Female
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Male
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Processing, Post-Translational
  • RNA Processing, Post-Transcriptional*
  • RNA, Long Noncoding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Untranslated / chemistry
  • RNA, Untranslated / genetics*
  • RNA-Binding Proteins / metabolism*
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Sequence Deletion / genetics
  • Serine-Arginine Splicing Factors
  • X Chromosome Inactivation / genetics*

Substances

  • Histones
  • Nuclear Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Untranslated
  • RNA-Binding Proteins
  • XIST non-coding RNA
  • Serine-Arginine Splicing Factors