Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65
10.1038/srep12521
Crossref journal-article
Springer Science and Business Media LLC
Scientific Reports (297)
Abstract

AbstractHuntington’s disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. Recent evidence suggests that HD is a consequence of multimodal, non-mutually exclusive mechanisms of pathogenesis that involve both HTT protein- and HTT RNA-triggered mechanisms. Here we provide further evidence for the role of expanded HTT (expHTT) RNA in HD by demonstrating that a fragment of expHTT is cytotoxic in the absence of any translation and that the extent of cytotoxicity is similar to the cytotoxicity of an expHTT protein fragment encoded by a transcript of similar length and with a similar repeat size. In addition, full-length (FL) expHTT is retained in the nucleus. Overexpression of the splicing factor muscleblind-like 1 (MBNL1) increases nuclear retention of expHTT and decreases the expression of expHTT protein in the cytosol. The splicing and nuclear export factor U2AF65 has the opposite effect, decreasing expHTT nuclear retention and increasing expression of expHTT protein. This suggests that MBNL1 and U2AF65 play a role in nuclear export of expHTT RNA.

Bibliography

Sun, X., Li, P. P., Zhu, S., Cohen, R., Marque, L. O., Ross, C. A., Pulst, S. M., Chan, H. Y. E., Margolis, R. L., & Rudnicki, D. D. (2015). Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65. Scientific Reports, 5(1).

Authors 10
  1. Xin Sun (first)
  2. Pan P. Li (additional)
  3. Shanshan Zhu (additional)
  4. Rachael Cohen (additional)
  5. Leonard O. Marque (additional)
  6. Christopher A. Ross (additional)
  7. Stefan M. Pulst (additional)
  8. Ho Yin Edwin Chan (additional)
  9. Russell L. Margolis (additional)
  10. Dobrila D. Rudnicki (additional)
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Dates
Type When
Created 10 years, 1 month ago (July 28, 2015, 8:58 a.m.)
Deposited 2 years, 7 months ago (Jan. 5, 2023, 9:28 a.m.)
Indexed 1 year ago (Aug. 26, 2024, 8:31 p.m.)
Issued 10 years, 1 month ago (July 28, 2015)
Published 10 years, 1 month ago (July 28, 2015)
Published Online 10 years, 1 month ago (July 28, 2015)
Funders 0

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@article{Sun_2015, title={Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65}, volume={5}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/srep12521}, DOI={10.1038/srep12521}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Sun, Xin and Li, Pan P. and Zhu, Shanshan and Cohen, Rachael and Marque, Leonard O. and Ross, Christopher A. and Pulst, Stefan M. and Chan, Ho Yin Edwin and Margolis, Russell L. and Rudnicki, Dobrila D.}, year={2015}, month=jul }