Altered Nuclear Retention of mRNAs Containing Inverted Repeats in Human Embryonic Stem Cells: Functional Role of a Nuclear Noncoding RNA
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, PS...
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Published in | Molecular cell Vol. 35; no. 4; pp. 467 - 478 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
28.08.2009
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Subjects | |
Online Access | Get full text |
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Summary: | 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 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1097-2765 1097-4164 |
DOI: | 10.1016/j.molcel.2009.06.027 |