期刊
RNA BIOLOGY
卷 8, 期 6, 页码 1084-1093出版社
LANDES BIOSCIENCE
DOI: 10.4161/rna.8.6.17015
关键词
7SK RNA; HMGA1; P-TEFb; cooperativity; transcription initiation; transcription elongation; HIV
资金
- ANR [Physiopath2007 ISPA]
- Genopole Evry
- Agence Nationale de echerche sur le SIDA et les hepatites virales (ANRS)
7SK small-nuclear RNA has been shown to negatively regulate P-TEFb transcription elongation on the one hand and control HMGA1 transcription initiation and chromatin remodeling on the other. The non-coding 7SK RNA thereby directly interacts with both factors through different regions. While the loop 2 of the RNA specifically binds to the first HMGA1 A/T hook, thereby competing with DNA binding to the same domain, loops 1, 3 and 4 are involved in P-TEFb interaction. This raises the question of whether HMGA1 and P-TEFb cooperate during gene transcription. Using transcriptome profiling, we have identifed genes that are oppositely regulated by 7SK RNA overexpression versus shRNA mediated knockdown. Inhibition of P-TEFb by competitive expression of a dominant-negative Cdk9 protein leads to highly similar changes in global gene expression as the overexpression of 7SK RNA, confirming the importance of P-TEFb inhibition by 7SK RNA. Furthermore, we have similarly assembled genes affected concomitantly by HMGA1 overexpression. HMGA1 and P-TEFb, in the case of select target genes, show strong cooperation in transcriptional activation. Finally, we provide evidence for 7SK RNA complexes containing simultaneously HMGA1 and P-TEFb. 7SK RNA thus establishes gene-dependent plasticity between HMGA1 chromatin remodeling and transcription initiation and P-TEFb transcription elongation.
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