Prokaryotic Argonautes(pAgos)provide bacteria and archaea with immunity against plasmids and viruses.Catalytically active pAgos utilize short oligonucleotides as guides to directly cleave foreign nucleic acids,while i...Prokaryotic Argonautes(pAgos)provide bacteria and archaea with immunity against plasmids and viruses.Catalytically active pAgos utilize short oligonucleotides as guides to directly cleave foreign nucleic acids,while inactive pAgos lacking catalytic residues employ auxiliary effectors,such as nonspecific nucleases,to trigger abortive infection upon detection of foreign nucleic acids.Here,we report a unique group of catalytically active pAgo proteins that frequently associate with a phos-pholipase D(PLD)family protein.We demonstrate that this particular system employs the catalytic center of the associated PLD protein rather than that of pAgo to restrict plasmid DNA,while interestingly,its immunity against a single-stranded DNA virus relies on the pAgo catalytic center and is enhanced by the PLD protein.We also find that this system selectively suppresses viral DNA propagation without inducing noticeable abortive infection outcomes.Moreover,the pAgo protein alone enhances gene editing,which is unexpectedly inhibited by the PLD protein.Our data highlight the ability of catalytically active pAgo proteins to employ auxiliary proteins to strengthen the targeted eradication of different genetic invaders and underline the trend of PLD nucleases to participate in host immunity.展开更多
小分子调控RNA,包括siRNA(small interfering RNA)、miRNA(microRNA)和piRNA(piwi interacting RNA)、hsRNA(heterochromatin associated small RNA)等,是当前生命科学研究的前沿热点。越来越多的证据表明,这些小分子R N A存在于几乎所...小分子调控RNA,包括siRNA(small interfering RNA)、miRNA(microRNA)和piRNA(piwi interacting RNA)、hsRNA(heterochromatin associated small RNA)等,是当前生命科学研究的前沿热点。越来越多的证据表明,这些小分子R N A存在于几乎所有较高等的真核生物细胞中,对生物体具有非常重要的调控功能。它们通过各种序列特异性的RNA基因沉默作用,包括RNA干扰(RNAi)、翻译抑制、异染色质形成等,调控诸如生长发育、应激反应、沉默转座子等各种各样的细胞进程。随着对这些小分子调控RNA的发现,一些RNase III酶家族成员、Argonaute蛋白质家族成员及RNA结合蛋白质等先后被鉴定为小RNA的胞内蛋白质合作者,参与小RNA的加工成熟和在细胞内行使功能。本综述简介一些RNA沉默作用途径中重要组分的结构和功能的研究进展。展开更多
基金This work was supported by the Science&Technology Fundamental Resources Investigation Program(2022FY101100)the Strategic Priority Research Program of the Chinese Academy of Sciences(Precision seed design and breeding)(XDA24020101)+4 种基金the National Natural Science Foundation of China(Nos.31970544,31970545,32022003,32150020,32200057,and 32270092)the Youth Innovation Promotion Association of CAS(No.2020090)the China National Postdoctoral Program for Innovative Talents(BX20220331)the China Postdoctoral Science Foundation(2022M720160)the Special Research Assistant Program of Chinese Academy of Sciences(No.2023000056).
文摘Prokaryotic Argonautes(pAgos)provide bacteria and archaea with immunity against plasmids and viruses.Catalytically active pAgos utilize short oligonucleotides as guides to directly cleave foreign nucleic acids,while inactive pAgos lacking catalytic residues employ auxiliary effectors,such as nonspecific nucleases,to trigger abortive infection upon detection of foreign nucleic acids.Here,we report a unique group of catalytically active pAgo proteins that frequently associate with a phos-pholipase D(PLD)family protein.We demonstrate that this particular system employs the catalytic center of the associated PLD protein rather than that of pAgo to restrict plasmid DNA,while interestingly,its immunity against a single-stranded DNA virus relies on the pAgo catalytic center and is enhanced by the PLD protein.We also find that this system selectively suppresses viral DNA propagation without inducing noticeable abortive infection outcomes.Moreover,the pAgo protein alone enhances gene editing,which is unexpectedly inhibited by the PLD protein.Our data highlight the ability of catalytically active pAgo proteins to employ auxiliary proteins to strengthen the targeted eradication of different genetic invaders and underline the trend of PLD nucleases to participate in host immunity.
