Science China Life Sciences, Год журнала: 2022, Номер 65(7), С. 1285 - 1324
Опубликована: Июнь 14, 2022
Язык: Английский
Nucleic Acids Research, Год журнала: 2022, Номер 50(14), С. 8168 - 8192
Опубликована: Июль 24, 2022
Abstract Nucleocapsid protein (N-protein) is required for multiple steps in betacoronaviruses replication. SARS-CoV-2-N-protein condenses with specific viral RNAs at particular temperatures making it a powerful model deciphering RNA sequence specificity condensates. We identify two separate and distinct double-stranded, motifs (dsRNA stickers) that promote N-protein condensation. These dsRNA stickers are separately recognized by N-protein's binding domains (RBDs). RBD1 prefers structured sequences like the transcription-regulatory (TRS). RBD2 long stretches of dsRNA, independent sequence. Thus, RBDs interact stickers, these interactions impart droplet physical properties could support varied functions. Specifically, we find addition lowers condensation temperature dependent on tunes translational repression. In contrast sites critical sub-genomic (sg) generation gRNA compression. The density proximity to TRS-L/B associated levels generation. switch packaging likely mediated which generate particles recapitulate unit virion. SARS-CoV-2 can achieve biochemical complexity, performing functions same cytoplasm, minimal components based utilizing control interactions.
Язык: Английский
Процитировано
65
Journal of the American Chemical Society, Год журнала: 2021, Номер 143(30), С. 11404 - 11422
Опубликована: Июль 20, 2021
The SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19. This small gene employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a 1b, which code viral polyproteins. Any interference with this process has profound effect on replication propagation. Pinpointing structures adapted by FSE associated structural transformations involved in been challenge. Using our graph-theory-based modeling tools representing secondary structures, "RAG" (RNA-As-Graphs), chemical structure probing experiments, we show that 3-stem H-type pseudoknot (3_6 dual graph), long assumed be dominant structure, viable alternative, HL-type (3_3) longer constructs. In addition, unknotted 3-way junction (3_5) emerges as minor conformation. These three conformations share Stems 1 3, while different Stem 2 may conformational switch possibly associations translation. For full-length genomes, stem-loop motif (2_2) compete these forms. mechanistic insights advance understanding of concomitant virus life cycle, point avenues intervention.
Язык: Английский
Процитировано
60
Frontiers in Microbiology, Год журнала: 2021, Номер 12
Опубликована: Сен. 28, 2021
Coronaviruses have brought severe challenges to public health all over the world in past 20years. SARS-CoV-2, causative agent of COVID-19 pandemic that has led millions deaths, belongs genus beta-coronavirus. Alpha- and beta-coronaviruses encode a unique protein, nonstructural protein 1 (Nsp1) both suppresses host immune responses reduces global gene expression levels cells. As key pathogenicity factor coronaviruses, Nsp1 redirects translation machinery increase synthesis viral proteins. Through multiple mechanisms, coronaviruses impede through Nsp1, while escaping inhibition allow RNA. In this review, we discuss current data about suppression induced by coronavirus as well prospect live-attenuated vaccine development with virulence-attenuated viruses mutations Nsp1.
Язык: Английский
Процитировано
60
Cell Reports, Год журнала: 2022, Номер 39(4), С. 110744 - 110744
Опубликована: Апрель 1, 2022
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 pandemic, which has led to a devastating global health crisis. The emergence variants that escape neutralizing responses emphasizes urgent need deepen our understanding SARS-CoV-2 biology. Using comprehensive identification RNA-binding proteins (RBPs) by mass spectrometry (ChIRP-MS) approach, we identify 107 high-confidence cellular factors interact with genome during infection. By systematically knocking down their expression in human lung epithelial cells, find majority identified RBPs are proviral factors. In particular, show HNRNPA2B1, ILF3, QKI, and SFPQ promote viral RNA amplification. Our study provides valuable resources for future investigations into mechanisms replication host-centered antiviral therapies.
Язык: Английский
Процитировано
54
Science China Life Sciences, Год журнала: 2022, Номер 65(7), С. 1285 - 1324
Опубликована: Июнь 14, 2022
Язык: Английский
Процитировано
44