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Pseudouridylation of 7 SK sn RNA promotes 7 SK sn RNP formation to suppress HIV ‐1 transcription and escape from latency
Author(s) -
Zhao Yang,
Karijolich John,
Glaunsinger Britt,
Zhou Qiang
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201642682
Subject(s) - latency (audio) , chemistry , transcription (linguistics) , rna , microbiology and biotechnology , biology , biochemistry , gene , computer science , telecommunications , philosophy , linguistics
The 7 SK sn RNA sequesters P‐ TEF b, a general transcription elongation factor and human co‐factor for HIV ‐1 Tat protein, into the catalytically inactive 7 SK sn RNP . Little is known about how 7 SK RNA is regulated to perform this function. Here, we show that most of 7 SK is pseudouridylated at position U250 by the predominant cellular pseudouridine synthase machinery, the DKC 1–box H/ ACA RNP . Pseudouridylation is critical to stabilize 7 SK sn RNP , as its abolishment by either mutation at or around U250 or depletion of DKC 1, the catalytic component of the box H/ ACA RNP , disrupts 7 SK sn RNP and releases P‐ TEF b to form the super elongation complex ( SEC ) and the Brd4–P‐ TEF b complex. The SEC is then recruited by Tat to the HIV ‐1 promoter to stimulate viral transcription and escape from latency. Thus, although 7 SK RNA levels remain mostly unchanged, its function is modulated by pseudouridylation, which in turn controls transcription of both HIV ‐1 and cellular genes.