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Altered Nuclear Retention of mRNAs Containing Inverted Repeats in Human Embryonic Stem Cells: Functional Role of a Nuclear Noncoding RNA
Open accessAbstract
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 p54nrb, PSF and PSP1α. We report that robust editing activity in human embryonic stem cells (hESCs), does not lead to nuclear retention. p54nrb, PSF and PSP1α are all expressed in hESCs, but paraspeckles are absent and only appear upon differentiation. Paraspeckle assembly and function depends on expression of a long nuclear-retained noncoding RNA, hNEAT1. This RNA is not expressed in hESCs, but is induced upon differentiation. Knockdown of hNEAT1 in HeLa cells results both in loss of paraspeckles and 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.
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Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
Clemson, C. M., Hutchinson, J. N., Sara, S. A., Ensminger, A. W., Fox, A. H., Chess, A., & Lawrence, J. B. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.01.026 · Cited by 1,445
Heterochronic Mutants of the Nematode Caenorhabditis elegans
Ambros, V., & Horvitz, H. R. (1984) · Science · doi:10.1126/science.6494891 · Cited by 797
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Batista, P. J., & Chang, H. Y. (2013) · Cell · doi:10.1016/j.cell.2013.02.012 · Cited by 2,531
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Cech, T. R., & Steitz, J. A. (2014) · Cell · doi:10.1016/j.cell.2014.03.008 · Cited by 2,524
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Kung, J. T. Y., Colognori, D., & Lee, J. T. (2013) · Genetics · doi:10.1534/genetics.112.146704 · Cited by 1,874
LNCcation: lncRNA localization and function
Bridges, M. C., Daulagala, A. C., & Kourtidis, A. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202009045 · Cited by 1,556
Alternative polyadenylation of mRNA precursors
Tian, B., & Manley, J. L. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.116 · Cited by 1,179
Metadata
- Authors
- Chen, L.-L., & Carmichael, G. G.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 35
- Issue
- 4
- Pages
- 467-478
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2065466457
- Cited by
- 659
- References
- 4
- FWCI
- 12.60
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chen, L.-L., & Carmichael, G. G. (2009). Altered Nuclear Retention of mRNAs Containing Inverted Repeats in Human Embryonic Stem Cells: Functional Role of a Nuclear Noncoding RNA. Molecular Cell. https://doi.org/10.1016/j.molcel.2009.06.027
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