The 7SK snRNA sequesters P‐TEFb, a general transcription elongation factor and human co‐factor for HIV‐1 Tat protein, into the catalytically inactive 7SK snRNP. Little is known about how 7SK RNA is regulated to perform this function. Here, we show that most of 7SK is pseudouridylated at position U250 by the predominant cellular pseudouridine synthase machinery, the DKC1–box H/ACA RNP. Pseudouridylation is critical to stabilize 7SK snRNP, as its abolishment by either mutation at or around U250 or depletion of DKC1, the catalytic component of the box H/ACA RNP, disrupts 7SK snRNP and releases P‐TEFb to form the super elongation complex (SEC) and the Brd4–P‐TEFb complex. The SEC is then recruited by Tat to the HIV‐1 promoter to stimulate viral transcription and escape from latency. Thus, although 7SK RNA levels remain mostly unchanged, its function is modulated by pseudouridylation, which in turn controls transcription of both HIV‐1 and cellular genes.
The 7SK RNA is an abundant non‐coding nuclear RNA that is highly conserved in vertebrates. This study indicates that its function can be modulated by pseudouridylation, which in turn controls transcription of both HIV‐1 and cellular genes.
The vast majority of cellular 7SK snRNA is pseudouridylated on U250 by the predominant cellular pseudouridine synthase machinery, the DKC1–box H/ACA RNP.
Pseudouridylation of 7SK RNA promotes formation of the 7SK snRNP that sequesters the general transcription elongation factor P‐TEFb into the catalytically inactive form to suppress HIV‐1 transcription and escape from latency.
- Received May 5, 2016.
- Revision received July 27, 2016.
- Accepted July 28, 2016.
- © 2016 The Authors