Nuclear receptors (NRs) induce transcription through association with coactivator complexes. We identified a pseudouridine synthase (PUS), mPus1p, as a coactivator for retinoic acid receptor (mRAR)gamma and other NR-dependent transactivation. mPus1p is a member of the truA subfamily of PUSs, a class of enzymes that isomerize uridine to pseudouridine in noncoding RNAs, such as tRNA, to ensure proper folding and function. mPus1p binds the first zinc finger of mRARgamma and also associates with other NRs. Interestingly, mPus1p pseudouridylates coactivator Steroid Receptor RNA Activator (SRA), and when coexpressed, mPus1p and SRA cooperatively enhance mRARgamma-mediated transcription. mPus1p, mRARgamma, and SRA exist in a retinoid-independent, promoter bound complex in the nucleus although mPus1p is also expressed in the nucleolus, where it likely modifies tRNA. Finally, we show that mPus1p-coactivator function required SRA, mPus1p-associated mRARgamma binding, and PUS activities. mPus1p-dependent pseudouridylation of SRA represents an additional type of posttranscriptional modification of a NR-coactivator complex that is important for NR signaling.
Abstractp53 is a critical tumor suppressor which removes cells with DNA damage by regulating expression and activity of a select group of p53-induced genes
Botfly larvae (Cuterebra sp.) infesting spiny rats (Proechimys semispinosus) in 8 small islands in the Panama Canal were studied. Rats were live trapped monthly on each island from January 1991 through February 2000 and visually examined for the presence of bots. Overall, bot prevalence was 4.6% and differed statistically among island rat populations. Rats were simultaneously infested by as many as 4 bots. Overall bot intensity was 1.3 bots per infested rat and did not differ among islands. Mean bot density across all islands was 0.0111 and was greater during the dry seasons than during the rainy seasons, but it did not differ among islands. Bots were found during all the 12 calendar months, suggesting a multivoltine reproductive schedule. Although bot activity varied seasonally, there was little synchrony of bot activity among islands. Bot density was related negatively to rainfall but was not related to host density, suggesting that drier ambient conditions may promote reproduction by adult bot flies in this system.
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