| Autor: |
Prasanth KV; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Camiolo M, Chan G, Tripathi V, Denis L, Nakamura T, Hübner MR, Spector DL |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular biology of the cell [Mol Biol Cell] 2010 Dec; Vol. 21 (23), pp. 4184-96. Date of Electronic Publication: 2010 Sep 29. |
| DOI: |
10.1091/mbc.E10-02-0105 |
| Abstrakt: |
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 enriched in pre-mRNA processing factors. 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 mislocalization 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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