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PABP-driven secondary condensed phase within RSV inclusion bodies activates viral mRNAs for ribosomal recruitment

作     者:Qiang Zhang Hanzhe Ye Cong Liu Haiwu Zhou Mingbin He Xiaodong Liang Yu Zhou Kun Wang Yali Qin Zhifei Li Mingzhou Chen 

作者机构:State Key Laboratory of Virology and Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhan430072China Taikang Center for Life and Medical SciencesWuhan UniversityWuhan430072China Hubei Jiangxia LaboratoryWuhan430200China 

出 版 物:《Virologica Sinica》 (中国病毒学(英文版))

年 卷 期:2024年第39卷第2期

页      面:235-250页

核心收录:

学科分类:0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基  金:supported by the grants from National Key R&D Program of China(2021YFC2300702 and 2021YFC2300200) the Hubei Provincial Natural Science Foundation of China(2021CFB364) the National Natural Science Foundation of China(82130064,81825015,U22A20337 and 32000119) the Key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory(JXBS001) 

主  题:Respiratory syncytial virus(RSV) Inclusion bodies(IBs) Biomolecular condensates Liquid-liquid phase separation(LLPS) Secondary condensed phase mRNA activation 

摘      要:Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules(IBAGs),where anti-termination factor M2-1 and viral mRNAs are ***,the mechanism of IBAG formation and the physiological function of IBAGs are ***,we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein(mRNP)condensates formed by secondary ***,the RSV nucleoprotein(N)and M2-1 interact with and recruit PABP to IBs,promoting PABP to bind viral mRNAs transcribed in IBs by RNArecognition motif and drive secondary phase ***,PABP-eIF4G1 interaction regulates viral mRNP condensate composition,thereby recruiting specific translation initiation factors(eIF4G1,eIF4E,eIF4A,eIF4B and eIF4H)into the secondary condensed phase to activate viral mRNAs for ribosomal *** study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.

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