Prasanth, K. V. , Camiolo, M., Chan, G., Tripathi, V., Denis, L., Nakamura, T., Hubner, M., Spector, D. L. (December 2010) Nuclear Organization and Dynamics of 7SK RNA in Regulating Gene Expression. Molecular Biology of the Cell, 21 (23). pp. 4184-4196. ISSN 1059-1524
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Abstract
Noncoding RNAs play important roles in various aspects of gene regulation. We have identified 7SK RNA to be enriched in nuclear speckles or interchromatin granule clusters (IGCs), a subnuclear domain involved in pre-mRNA processing. 7SK RNA, in association with HEXIM 1 and 2, is involved in the inhibition of transcriptional elongation by RNA polymerase II. Inhibition occurs via sequestration of the active P-TEFb kinase complex (CDK 9 and Cyclin T1/T2a/b or K) that is involved in phosphorylating the C-terminal domain of RNA polymerase II. Our results demonstrate that knock-down of 7SK RNA, by specific antisense oligonucleotides, results in the mis-localization of nuclear speckle constituents in a transcription-dependent manner, and the transcriptional up-regulation of a RNA polymerase II transcribed reporter gene locus. Furthermore, 7SK RNA transiently associates with a stably integrated reporter gene locus upon transcriptional down-regulation and its presence correlates with the efficient displacement of P-TEFb constituents from the locus. Our results suggest that 7SK RNA plays a role in modulating the available level of P-TEFb upon transcriptional down-regulation by sequestering its constituents in nuclear speckles.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > antisense bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > ncRNA |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Shared Resources > DNA Sequencing Service CSHL Cancer Center Shared Resources > Microscopy Service CSHL labs > Spector lab CSHL Cancer Center Program > Gene Regulation and Cell Proliferation |
| Depositing User: | CSHL Librarian |
| Date: | 1 December 2010 |
| Date Deposited: | 05 Oct 2011 13:32 |
| Last Modified: | 13 Oct 2015 16:12 |
| PMCID: | PMC2993747 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/15508 |
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