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首页> 外文期刊>Molecular and Cellular Biology >The Transcription-Dependent Dissociation of P-TEFb-HEXIM1-7SK RNA Relies upon Formation of hnRNP-7SK RNA Complexes
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The Transcription-Dependent Dissociation of P-TEFb-HEXIM1-7SK RNA Relies upon Formation of hnRNP-7SK RNA Complexes

机译：P-TEFb-HEXIM1-7SK RNA的转录依赖性解离依赖于hnRNP-7SK RNA复合物的形成。

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摘要

The positive transcription elongation factor P-TEFb controls the elongation of transcription by RNA polymerase II. P-TEFb is inactivated upon binding to HEXIM1 or HEXIM2 proteins associated with a noncoding RNA, 7SK. In response to the inhibition of transcription, 7SK RNA, as well as HEXIM proteins, is released by an unknown mechanism and P-TEFb is activated. New partners of 7SK RNA were searched for as potential players in this feedback process. A subset of heterogeneous ribonuclear proteins, hnRNPs Q and R and hnRNPs A1 and A2, were thus identified as major 7SK RNA-associated proteins. The degree of association of 7SK RNA with these hnRNPs increased when P-TEFb-HEXIM1-7SK was dissociated following the inhibition of transcription or HEXIM1 knockdown. This finding suggested that 7SK RNA shuttles from HEXIM1-P-TEFb complexes to hnRNPs. The transcription-dependent dissociation of P-TEFb-HEXIM1-7SK complexes was attenuated when both hnRNPs A1 and A2 were knocked down by small interfering RNA. As hnRNPs are known to interact transiently with RNA while it is synthesized, hnRNPs released from nascent transcripts may trap 7SK RNA and thereby contribute to the activation of P-TEFb.
机译：正转录延长因子P-TEFb控制RNA聚合酶II的转录延长。结合与非编码RNA 7SK相关的HEXIM1或HEXIM2蛋白后，P-TEFb失活。响应转录抑制，未知机制释放了7SK RNA以及HEXIM蛋白，并激活了P-TEFb。寻找7SK RNA的新伙伴作为该反馈过程中的潜在参与者。异源核糖核酸蛋白的一个子集，hnRNP Q和R和hnRNP A1和A2，因此被确定为主要的7SK RNA相关蛋白。当P-TEFb-HEXIM1-7SK在抑制转录或敲除HEXIM1后解离时，7SK RNA与这些hnRNP的缔合度增加。这一发现表明7SK RNA从HEXIM1-P-TEFb复合体穿梭到hnRNPs。当hnRNPs A1和A2均被小干扰RNA击倒时，P-TEFb-HEXIM1-7SK复合物的转录依赖性解离减弱。由于已知hnRNP在合成时会与RNA短暂相互作用，因此从新生转录本释放的hnRNP可能会捕获7SK RNA，从而有助于P-TEFb的激活。

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