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

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Abstract:

In mammalian cells, some mRNAs containing inverted repeats in their 3’-untranslated regions (3’-UTRs) are inefficiently exported to the cytoplasm, leading to disproportionate nuclear accumulation. This nuclear retention is associated with adenosine-to-inosine RNA editing and is found in paraspeckle-associated complexes containing the proteins p54nrb, PSF and PSP1α.  In humans many such retained mRNAs likely contain inverted Alu repeats in their 3’-UTRs. We have found that in human embryonic stem cells (hESCs), editing activity is robust but the nuclear retention pathway is not operational.  p54nrb, PSF and PSP1α are all expressed in hESCs, but paraspeckles are absent and only appear as cells differentiate. Paraspeckle assembly and function depends on the 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 in both the loss of paraspeckles and the enhanced nucleocytoplasmic export of mRNAs containing inverted Alu repeats in their 3’-UTRs.  Taken together, these results assign a novel biological function to a large noncoding nuclear RNA and also demonstrate that hESCs allow the nucleocytoplasmic export of structured mRNAs that are retained in the nuclei of differentiated cells.
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Association:
Name: Connecticut's Stem Cell Research International Symposium
URL:
http://stemconn.org


Citation:
URL: http://citation.allacademic.com/meta/p319312_index.html
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MLA Citation:

Chen, Ling-Ling. and Carmichael, Gordon. "Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: Functional role of a nuclear noncoding RNA" Paper presented at the annual meeting of the Connecticut's Stem Cell Research International Symposium, Omni Hotel, New Haven, CT, Mar 23, 2009 <Not Available>. 2014-11-29 <http://citation.allacademic.com/meta/p319312_index.html>

APA Citation:

Chen, L. and Carmichael, G. , 2009-03-23 "Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: Functional role of a nuclear noncoding RNA" Paper presented at the annual meeting of the Connecticut's Stem Cell Research International Symposium, Omni Hotel, New Haven, CT <Not Available>. 2014-11-29 from http://citation.allacademic.com/meta/p319312_index.html

Publication Type: Poster
Review Method: Peer Reviewed
Abstract: In mammalian cells, some mRNAs containing inverted repeats in their 3’-untranslated regions (3’-UTRs) are inefficiently exported to the cytoplasm, leading to disproportionate nuclear accumulation. This nuclear retention is associated with adenosine-to-inosine RNA editing and is found in paraspeckle-associated complexes containing the proteins p54nrb, PSF and PSP1α.  In humans many such retained mRNAs likely contain inverted Alu repeats in their 3’-UTRs. We have found that in human embryonic stem cells (hESCs), editing activity is robust but the nuclear retention pathway is not operational.  p54nrb, PSF and PSP1α are all expressed in hESCs, but paraspeckles are absent and only appear as cells differentiate. Paraspeckle assembly and function depends on the 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 in both the loss of paraspeckles and the enhanced nucleocytoplasmic export of mRNAs containing inverted Alu repeats in their 3’-UTRs.  Taken together, these results assign a novel biological function to a large noncoding nuclear RNA and also demonstrate that hESCs allow the nucleocytoplasmic export of structured mRNAs that are retained in the nuclei of differentiated cells.


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