The Drosophila 7SK snRNP and the essential role of dHEXIM in development

Duy Nguyen; Brian J Krueger; Stanley C Sedore; John E Brogie; Jason T Rogers; T K Rajendra; Abbie Saunders; A Greg Matera; John T Lis; Patricia Uguen; David H Price

doi:10.1093/nar/gks191

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The Drosophila 7SK snRNP and the essential role of dHEXIM in development

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The Drosophila 7SK snRNP and the essential role of dHEXIM in development

Duy Nguyen, Brian J Krueger, Stanley C Sedore, John E Brogie, Jason T Rogers, T K Rajendra, Abbie Saunders, A Greg Matera, John T Lis, Patricia Uguen, …

Nucleic acids research, Vol.40(12), pp.5283-5297

07/2012

DOI: 10.1093/nar/gks191

PMCID: PMC3384314

PMID: 22379134

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Abstract

Regulation of the positive transcription elongation factor, P-TEFb, plays a major role in controlling mammalian transcription and this is accomplished in part by controlled release of P-TEFb from the 7SK snRNP that sequesters the kinase in an inactive state. We demonstrate here that a similar P-TEFb control system exists in Drosophila. We show that an RNA previously suggested to be a 7SK homolog is, in fact, associated with P-TEFb, through the action of a homolog of the human HEXIM1/2 proteins (dHEXIM). In addition, a Drosophila La related protein (now called dLARP7) is shown to be the functional homolog of human LARP7. The Drosophila 7SK snRNP (d7SK snRNP) responded to treatment of cells with P-TEFb inhibitors and to nuclease treatment of cell lysates by releasing P-TEFb. Supporting a critical role for the d7SK snRNP in Drosophila development, dLARP7 and dHEXIM were found to be ubiquitously expressed throughout embryos and tissues at all stages. Importantly, knockdown of dHEXIM was embryonic lethal, and reduction of dHEXIM in specific tissues led to serious developmental defects. Our results suggest that regulation of P-TEFb by the d7SK snRNP is essential for the growth and differentiation of tissues required during Drosophila development.

Amino Acid Sequence

Cell Line

Drosophila melanogaster - embryology

RNA-Binding Proteins - physiology

RNA-Binding Proteins - chemistry

Embryonic Development - genetics

Molecular Sequence Data

Ribonucleoproteins, Small Nuclear - genetics

Drosophila Proteins - chemistry

Positive Transcriptional Elongation Factor B - metabolism

Drosophila Proteins - metabolism

Drosophila melanogaster - genetics

Drosophila Proteins - physiology

Animals

Base Sequence

Drosophila melanogaster - growth & development

RNA-Binding Proteins - metabolism

Ribonucleoproteins, Small Nuclear - metabolism

Details

Title: Subtitle: The Drosophila 7SK snRNP and the essential role of dHEXIM in development
Creators: Duy Nguyen - Université Paris-Sud 11, UMR-S757, Bât. 443, Orsay, F-91405, INSERM, Orsay, F-91405, France
Brian J Krueger
Stanley C Sedore
John E Brogie
Jason T Rogers
T K Rajendra
Abbie Saunders
A Greg Matera
John T Lis
Patricia Uguen
David H Price
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.40(12), pp.5283-5297
Publisher: England
DOI: 10.1093/nar/gks191
PMID: 22379134
PMCID: PMC3384314
ISSN: 0305-1048
eISSN: 1362-4962
Grant note: GM25232 / NIGMS NIH HHS GM053034 / NIGMS NIH HHS GM35500 / NIGMS NIH HHS R01 GM053034 / NIGMS NIH HHS T32 GM007337 / NIGMS NIH HHS R01 GM035500 / NIGMS NIH HHS
Language: English
Date published: 07/2012
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9984024516202771

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