PMID:17925858
| Citation |
Young, TM, Tsai, M, Tian, B, Mathews, MB and Pe'ery, T (2007) Cellular mRNA activates transcription elongation by displacing 7SK RNA. PLoS ONE 2:e1010 |
|---|---|
| Abstract |
The positive transcription elongation factor P-TEFb is a pivotal regulator of gene expression in higher cells. Originally identified in Drosophila, attention was drawn to human P-TEFb by the discovery of its role as an essential cofactor for HIV-1 transcription. It is recruited to HIV transcription complexes by the viral transactivator Tat, and to cellular transcription complexes by a plethora of transcription factors. P-TEFb activity is negatively regulated by sequestration in a complex with the HEXIM proteins and 7SK RNA. The mechanism of P-TEFb release from the inhibitory complex is not known. We report that P-TEFb-dependent transcription from the HIV promoter can be stimulated by the mRNA encoding HIC, the human I-mfa domain-containing protein. The 3'-untranslated region of HIC mRNA is necessary and sufficient for this action. It forms complexes with P-TEFb and displaces 7SK RNA from the inhibitory complex in cells and cell extracts. A 314-nucleotide sequence near the 3' end of HIC mRNA has full activity and contains a predicted structure resembling the 3'-terminal hairpin of 7SK that is critical for P-TEFb binding. This represents the first example of a cellular mRNA that can regulate transcription via P-TEFb. Our findings offer a rationale for 7SK being an RNA transcriptional regulator and suggest a practical means for enhancing gene expression. |
| Links |
PubMed PMC1995758 Online version:10.1371/journal.pone.0001010 |
| Keywords |
3' Untranslated Regions; Animals; COS Cells; Cercopithecus aethiops; DNA, Complementary/metabolism; Gene Expression Regulation; HIV/metabolism; HIV Long Terminal Repeat; HIV-1/genetics; HeLa Cells; Humans; Mice; NIH 3T3 Cells; Positive Transcriptional Elongation Factor B/genetics; Promoter Regions, Genetic; RNA, Messenger/biosynthesis; RNA, Messenger/genetics; RNA, Messenger/metabolism; Transcription, Genetic |
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