Article | Published:

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

Nature Structural & Molecular Biology volume 17, pages 948954 (2010) | Download Citation

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.

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Acknowledgements

We thank K. Worringer, J. Huff, T. Fazzio, M.K. Alexander, L. Spector, P. O'Farrell and I. Listerman for critical reading of the manuscript, X.-D. Fu and S. Lin (University of California, San Diego) for tet-repressible ASF/SF2 cells, N. Krogan for mass spectrometry and A. Krainer (Cold Spring Harbor) for ASF/SF2 antibodies. This work was funded in part by US National Institutes of Health grant R01 GM088506.

Author information

Author notes

    • Morgan E Royce-Tolland
    •  & Angela A Andersen

    These authors contributed equally to this work.

Affiliations

  1. Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA.

    • Morgan E Royce-Tolland
    • , Hannah R Koyfman
    • , Dale J Talbot
    •  & Barbara Panning
  2. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.

    • Angela A Andersen
  3. The Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, UK.

    • Anton Wutz
  4. Queensland Institute of Medical Research, Brisbane, Australia.

    • Ian D Tonks
    •  & Graham F Kay

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Contributions

M.E.R.-T., A.A.A., H.R.K., D.J.T. and B.P. designed and performed experiments and wrote the manuscript, and A.W., I.D.T. and G.F.K. provided cell lines.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Barbara Panning.

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DOI

https://doi.org/10.1038/nsmb.1877

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