Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA

Mol Cell. 2009 Aug 28;35(4):467-78. doi: 10.1016/j.molcel.2009.06.027.

Abstract

In many cells, mRNAs containing inverted repeats (Alu repeats in humans) in their 3' untranslated regions (3'UTRs) are inefficiently exported to the cytoplasm. Nuclear retention correlates with adenosine-to-inosine editing and is in paraspeckle-associated complexes containing the proteins p54(nrb), PSF, and PSP1 alpha. We report that robust editing activity in human embryonic stem cells (hESCs) does not lead to nuclear retention. p54(nrb), PSF, and PSP1 alpha are all expressed in hESCs, but paraspeckles are absent and only appear upon differentiation. Paraspeckle assembly and function depend on expression of a long nuclear-retained noncoding RNA, NEAT1. This RNA is not detectable in hESCs but is induced upon differentiation. Knockdown of NEAT1 in HeLa cells results both in loss of paraspeckles and in enhanced nucleocytoplasmic export of mRNAs containing inverted Alu repeats. Taken together, these results assign a biological function to a large noncoding nuclear RNA in the regulation of mRNA export.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Active Transport, Cell Nucleus
  • Adenosine Deaminase / metabolism
  • Alu Elements
  • Base Sequence
  • Cell Differentiation / genetics
  • Cell Nucleus / metabolism*
  • Cell Nucleus Structures / metabolism
  • Cells, Cultured
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Regulation, Developmental*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Nuclear Matrix-Associated Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Octamer Transcription Factors / metabolism
  • PTB-Associated Splicing Factor
  • RNA Editing*
  • RNA Interference
  • RNA, Messenger / metabolism*
  • RNA, Nuclear / metabolism*
  • RNA, Untranslated / metabolism*
  • RNA-Binding Proteins / metabolism

Substances

  • 3' Untranslated Regions
  • NONO protein, human
  • Nuclear Matrix-Associated Proteins
  • Nuclear Proteins
  • Octamer Transcription Factors
  • PSPC1 protein, human
  • PTB-Associated Splicing Factor
  • RNA, Messenger
  • RNA, Nuclear
  • RNA, Untranslated
  • RNA-Binding Proteins
  • ADARB1 protein, human
  • Adenosine Deaminase