The transcription-dependent dissociation of P-TEFb-HEXIMI-7SK RNA relies upon formation of hnRNP-7SK RNA complexes
The transcription-dependent dissociation of P-TEFb-HEXIMI-7SK RNA relies upon formation of hnRNP-7SK RNA complexes
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DOI：
10.1128/mcb.00975-07
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发表时间：
2007-10-01
影响因子：
5.3
通讯作者：
Bensaude, Olivier
中科院分区：
文献类型：
--
作者：
Barrandon, Charlotte;Bonnet, Francois;Bensaude, Olivier
正转录延伸因子P-TEFb控制RNA聚合酶II转录的延伸。P-TEFb在与非编码RNA 7SK相关的HEXIM 1或HEXIM 2蛋白结合后失活。作为对转录抑制的响应，7SK RNA以及HEXIM蛋白通过未知机制释放，并且P-TEFb被激活。在这个反馈过程中，寻找7SK RNA的新合作伙伴作为潜在的参与者。一个子集的异质核糖核蛋白，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-HEXIM 1 -7SK在转录抑制或HEXIM 1敲低后解离时，7SK RNA与这些hnRNP的缔合程度增加。这一发现表明7SK RNA从HEXIM 1-P-TEFb复合物穿梭到hnRNP。当hnRNP A1和A2被小干扰RNA敲低时，P-TEFb-HEXIM 1 -7SK复合物的转录依赖性解离减弱。由于已知hnRNP在RNA合成时与RNA瞬时相互作用，因此从新生转录物释放的hnRNP可以捕获7SK RNA，从而有助于P-TEFb的活化。
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.