title: The Drosophila 7SK snRNP and the essential role of dHEXIM in development.
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.
authors.affiliation: Université Paris-Sud 11, UMR-S757, Bât. 443, Orsay, F-91405, INSERM, Orsay, F-91405, France.
authors.forename: Duy
authors.initials: D
authors.lastname: Nguyen
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Krueger
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Sedore
authors.forename: John E
authors.initials: JE
authors.lastname: Brogie
authors.forename: Jason T
authors.initials: JT
authors.lastname: Rogers
authors.forename: T K
authors.initials: TK
authors.lastname: Rajendra
authors.forename: Abbie
authors.initials: A
authors.lastname: Saunders
authors.forename: A Greg
authors.initials: AG
authors.lastname: Matera
authors.forename: John T
authors.initials: JT
authors.lastname: Lis
authors.forename: Patricia
authors.initials: P
authors.lastname: Uguen
authors.forename: David H
authors.initials: DH
authors.lastname: Price
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000254:growth & development*; D047108:Embryonic Development / Q000235:genetics; D008969:Molecular Sequence Data; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C575290:HEXIM protein, Drosophila; C575291:LARP7 protein, Drosophila; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D042925:Positive Transcriptional Elongation Factor B