TY - JOUR
T1 - PABP-driven secondary condensed phase within RSV inclusion bodies activates viral mRNAs for ribosomal recruitment
AU - Zhang, Qiang
AU - Ye, Hanzhe
AU - Liu, Cong
AU - Zhou, Haiwu
AU - He, Mingbin
AU - Liang, Xiaodong
AU - Zhou, Yu
AU - Wang, Kun
AU - Qin, Yali
AU - Li, Zhifei
AU - Chen, Mingzhou
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2024/4
Y1 - 2024/4
N2 - 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 concentrated. However, the mechanism of IBAG formation and the physiological function of IBAGs are unclear. Here, we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein (mRNP) condensates formed by secondary LLPS. Mechanistically, the RSV nucleoprotein (N) and M2-1 interact with and recruit PABP to IBs, promoting PABP to bind viral mRNAs transcribed in IBs by RNA-recognition motif and drive secondary phase separation. Furthermore, 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 recruitment. Our study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.
AB - 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 concentrated. However, the mechanism of IBAG formation and the physiological function of IBAGs are unclear. Here, we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein (mRNP) condensates formed by secondary LLPS. Mechanistically, the RSV nucleoprotein (N) and M2-1 interact with and recruit PABP to IBs, promoting PABP to bind viral mRNAs transcribed in IBs by RNA-recognition motif and drive secondary phase separation. Furthermore, 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 recruitment. Our study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.
KW - Biomolecular condensates
KW - Inclusion bodies (IBs)
KW - Liquid-liquid phase separation (LLPS)
KW - Respiratory syncytial virus (RSV)
KW - Secondary condensed phase
KW - mRNA activation
UR - https://www.scopus.com/pages/publications/85182384931
U2 - 10.1016/j.virs.2023.12.001
DO - 10.1016/j.virs.2023.12.001
M3 - 文章
C2 - 38072230
AN - SCOPUS:85182384931
SN - 1674-0769
VL - 39
SP - 235
EP - 250
JO - Virologica Sinica
JF - Virologica Sinica
IS - 2
ER -
