例如:"lncRNA", "apoptosis", "WRKY"

The double-stranded RNA-binding protein, PACT, is required for postnatal anterior pituitary proliferation.

Proc. Natl. Acad. Sci. U.S.A.2009 Jun 30;106(26):10696-701. Epub 2009 Jun 17
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摘要


PACT is a double-stranded RNA-binding protein that also binds and activates the latent protein kinase, PKR, which plays a major role in cellular antiviral defense in mammals. For evaluating PACT's contribution to the innate immune system, Pact(-/-) mice have been generated; these mice exhibit notable developmental abnormalities including microtia, with craniofacial, ear, and hearing defects. Here we report that, in addition, Pact(-/-) mice had smaller body size and fertility defects, both of which were caused by defective pituitary functions. Pact(-/-) mice exhibited anterior pituitary lobe (AL) hypoplasia, which developed postnatally, when the second phase of pituitary expansion occurs. Among the 5 cell types in AL, the numbers of corticotrophs, gonadotrophs, and somatotrophs were equally decreased in Pact(-/-) mice with a greater impact on lactotrophs and a lesser impact on thyrotrophs. PACT mRNA and protein were highly expressed in the pituitary of wild-type (Wt) mice during the postnatal wave of AL proliferation, the same period in which the hypoplasia developed in Pact(-/-) mice. During this time, the pituitaries of Pact(-/-) mice did not exhibit significantly increased apoptosis compared with Wt mice but showed a decrease in cell proliferation. The inhibition of cell proliferation observed in vivo could be recapitulated in vitro in GH3 somato/lactotroph and LbetaT2 gonadotroph cell lines; knockdown of PACT expression with siRNA diminished the rate of proliferation of these cells. Our study revealed a physiologically significant role for PACT in cell proliferation and an essential role of a dsRNA-binding protein in mammalian pituitary expansion.

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