Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing.
Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing.
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HNRNP K和NS1-BP在流感和人mRNA剪接中的共调节活性。
DOI：
10.1038/s41467-018-04779-4
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发表时间：
2018-06-19
影响因子：
16.6
通讯作者：
Lynch KW
中科院分区：
文献类型：
--
作者：
Thompson MG;Muñoz-Moreno R;Bhat P;Roytenberg R;Lindberg J;Gazzara MR;Mallory MJ;Zhang K;García-Sastre A;Fontoura BMA;Lynch KW
由甲型流感病毒（IAV）编码的八个RNA片段中的三个经历选择性剪接以产生不同的蛋白质。以前，我们发现宿主蛋白hnRNP K和NS 1-BP调节IAV M片段的剪接，但其机制尚不清楚。我们发现NS 1-BP和hnRNP K在M2 5′剪接位点（5′ss）下游结合M mRNA。NS 1-BP结合最接近5′ss，部分重叠U1 snRNP结合位点，而hnRNP K结合更下游，促进U1 snRNP募集。hnRNP K和NS 1-BP结合位点之一或两者的突变导致M片段错误剪接和减弱的IAV复制。此外，我们表明，hnRNP K和NS 1-BP调节宿主剪接事件和病毒感染导致这些转录错误剪接。因此，我们提出的hnRNP K/NS 1-BP介导的IAV M剪接机制提供了抗病毒干预的潜在靶点，并揭示了这些蛋白质的新宿主功能。甲型流感病毒（IAV）M基因转录物的选择性剪接受hnRNP K和NS 1-BP的调控，但具体机制尚不清楚。在这里，Thompson等人展示了hnRNP K和NS 1-BP如何结合M mRNA，以及这些蛋白质在存在和不存在IAV感染的情况下调节宿主转录物的剪接。
Three of the eight RNA segments encoded by the influenza A virus (IAV) undergo alternative splicing to generate distinct proteins. Previously, we found that host proteins hnRNP K and NS1-BP regulate IAV M segment splicing, but the mechanistic details were unknown. Here we show NS1-BP and hnRNP K bind M mRNA downstream of the M2 5′ splice site (5′ss). NS1-BP binds most proximal to the 5′ss, partially overlapping the U1 snRNP binding site, while hnRNP K binds further downstream and promotes U1 snRNP recruitment. Mutation of either or both the hnRNP K and NS1-BP-binding sites results in M segment mis-splicing and attenuated IAV replication. Additionally, we show that hnRNP K and NS1-BP regulate host splicing events and that viral infection causes mis-splicing of some of these transcripts. Therefore, our proposed mechanism of hnRNP K/NS1-BP mediated IAV M splicing provides potential targets of antiviral intervention and reveals novel host functions for these proteins. Alternative splicing of influenza A virus (IAV) M transcript is regulated by hnRNP K and NS1-BP, but mechanistic details are unknown. Here, Thompson et al. show how hnRNP K and NS1-BP bind M mRNA and that these proteins regulate splicing of host transcripts in both the absence and presence of IAV infection.
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影响因子：
10.5
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