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Protein Cell:北京大学陈匡时课题组发表microRNA非特异性抵御逆转录病毒复制研究进展

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摘要 : 2017年9月7日,国际知名学术期刊《Protein & Cell》在线发表了北京大学工学院生物医学工程系陈匡时课题组的一篇研究论文,研究发现了宿主细胞抵御逆转录病毒感染的新机制

2017年9月7日,国际知名学术期刊《Protein & Cell》在线发表了北京大学工学院生物医学工程系陈匡时课题组的一篇研究论文,研究发现了宿主细胞抵御逆转录病毒感染的新机制。论文第一作者是曲娜,通讯作者为陈匡时特聘研究员。

以往的多数研究显示, micrornA可以通过与RNA-induced silencing complex(RISC)结合,从而靶向信使RNA(mRNA),发挥基因沉默功能。近年来,越来越多的研究结果显示microRNA也能够与RISC以外的蛋白质相互作用,发挥特定的调控、转运和信号转导等功能。例如,陈匡时课题组在2014年发表的研究成果显示,microRNA与HIV-1病毒组装蛋白(Group-specific antigen,Gag)结合形成microRNA-Gag复合体,该复合体能够阻断Gag与病毒RNA支架的相互作用,破坏Gag组装平台,使病毒颗粒无法有效释放。随后,组装失败的Gag复合体被细胞内吞形成囊泡,最终转运到溶酶体进行降解。通过荧光显微镜技术、细胞生物学、生物化学和电镜等手段,该课题组最新的研究发现,相同的microRNA干扰机制可能在其他逆转录病毒(如MLV)颗粒形成中发挥作用,还阐明了自噬相关蛋白质LC3、ATG5等在Gag囊泡形成中发挥作用,提示了自噬机制对于介导Gag复合体降解有决定性的角色。这一新机制有望为艾滋病或其它逆转录病毒疾病的治疗提供新的思路,并对探究其他RNA介导的蛋白质组装的调控过程具有重要启示。

Protein Cell:北京大学陈匡时课题组发表microRNA非特异性抵御逆转录病毒复制研究进展
 

microRNA(MiR+)-Gag复合体造成病毒颗粒组装失败并通过LC3、p62、ULK1、ATG5等自噬相关分子介导病毒在溶酶体中降解


原文链接:

Inhibition of retroviral Gag assembly by non-silencing miRNAs promotes autophagic viral degradation

原文摘要:

We recently reported an unconventional mechanism by which miRNAs inhibit HIV-1 viral production. This occurs when miRNAs bind nonspecifically to the viral structural protein Gag, interfering with viral RNA-mediated Gag assembly at the plasma membrane. Consequently, misassembled viral complexes are redirected into the endocytic pathway where they are delivered to lysosomes for degradation. In this study, we demonstrate that autophagy is a critical mediator of the viral degradation pathway and that this pathway is not HIV-1 specific. Misassembled viral complexes were found to colocalize extensively with LC3 and p62 in late endosomes/lysosomes, demonstrating a convergence of autophagy with functional degradative compartments. Knocking down autophagosome formation machineries reduced this convergence, while treatment with autophagy-inducer rapamycin enhanced the convergence. Furthermore, similar autophagy-dependent nonspecific miRNA inhibition of murine leukemia virus (MLV) assembly was shown. Overall, these results reveal autophagy as a crucial regulator of the retroviral degradation pathway in host cells initiated by nonspecific miRNA-Gag interactions. These findings could have significant implications for understanding how cells may regulate retroviral complex assembly by miRNA expression and autophagy, and raise the possibility that similar regulations can occur in other biological contexts.

doi:10.1007/s13238-017-0461-z

作者:陈匡时 点击:

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