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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.

SUBMITTER: Nguyen D

PROVIDER: S-EPMC3384314 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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

Nguyen Duy D Krueger Brian J BJ Sedore Stanley C SC Brogie John E JE Rogers Jason T JT Rajendra T K TK Saunders Abbie A Matera A Greg AG Lis John T JT Uguen Patricia P Price David H DH

Nucleic acids research 20120229 12

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 ( ...[more]

PMID: 22379134

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Project description:BackgroundThe protective external cuticle of insects does not accommodate growth during development. To compensate for this, the insect life cycle is punctuated by a series of molts. During the molt, a new and larger cuticle is produced underneath the old cuticle. Replacement of the smaller, old cuticle culminates with ecdysis, a stereotyped sequence of shedding behaviors. Following each ecdysis, the new cuticle must expand and harden. Studies from a variety of insect species indicate that this cuticle hardening is regulated by the neuropeptide bursicon. However, genetic evidence from Drosophila melanogaster only supports such a role for bursicon after the final ecdysis, when the adult fly emerges. The research presented here investigates the role that bursicon has at stages of Drosophila development which precede adult ecdysis.ResultsWe addressed the mechanism and timing of hormonal release from bursicon-positive motor neurons at the larval neuromuscular junction. Our findings indicate that vesicle membrane proteins which are required for classical neurotransmitter release are also expressed at these peptidergic motor neuron terminals; and that these terminals secrete hormones including bursicon at the neuromuscular junction, coinciding with larval ecdysis. This release surprisingly occurs in two waves, indicating bursicon secretion preceding and following the ecdysis sequence. Next, we addressed the functional significance of bursicon signaling during development, by disrupting the expression of its receptor, rickets, in different target tissues. We determined that rickets is developmentally required in the epidermis and imaginal discs for proper formation of the prepupa. It is also required to harden the pharate adult cuticle before eclosion. Significantly, we have also found that the available rickets mutants are not genetic nulls as previously believed, which necessitated the use of targeted RNA interference to disrupt rickets expression.ConclusionsOur results are consistent with the view that bursicon is the insect tanning hormone. However, this is the first study to rigorously demonstrate both its release and function during development. Importantly, we provide new evidence that bursicon release can precede the initiation of larval ecdysis, and that bursicon tans the puparium. Our results firmly establish bursicon signaling as essential to insect growth and development.

Dataset Information

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

Publications

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

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