The G-quadruplex(G4)sequences are short fragments of 4-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences are usually folded into secondary“knot”st...The G-quadruplex(G4)sequences are short fragments of 4-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences are usually folded into secondary“knot”structure via Hoogsteen hydrogen bond to exert negative regulation on a variety of biological processes,including DNA replication and transcription,mRNA translation,and telomere maintenance.Recent structural biological and mouse genetics studies have demonstrated that RHAU(DHX36)can bind and unwind the G4“knots”to modulate embryonic development and postnatal organ function.Deficiency of RHAU gives rise to embryonic lethality,impaired organogenesis,and organ dysfunction.These studies uncovered the pivotal G4 resolvase function of RHAU to release the G4 barrier,which plays fundamental roles in development and physiological homeostasis.This review discusses the latest advancements and findings in deciphering RHAU functions using animal models.展开更多
Genomic surveillance of monkeypox virus(MPXV)is essential to explore the reason of its unusual outbreak.Current phylogenomic analysis of the MPXV genome mainly focuses on the effect of amino acid mutations.Herein,we e...Genomic surveillance of monkeypox virus(MPXV)is essential to explore the reason of its unusual outbreak.Current phylogenomic analysis of the MPXV genome mainly focuses on the effect of amino acid mutations.Herein,we explore the evolutionary variation of RNA G-quadruplex(RG4)of MPXV and find that the genome evolution of MPXV can also produce new effects through changes in the RG4 structure.This RG4 is located in MPXV’s only Kelch-like C9L gene,which encodes for an antagonist of the innate immune response.The evolution of this virus increases the unfolding kinetic constant of C9L RG4 and promotes the C9 protein level in living cells.Importantly,all reported MPXV genomes in 2022 carry the C9L-RG4-5 pattern with the highest unfolding kinetic constant.Additionally,the RG4 ligand,RGB-1,can impede the unfolding of C9L-RG4-5 and thereby reduce the C9 protein level.These findings carve out a new path to comprehensively understanding MPXV virology.展开更多
基金National Key Research and Development Program of ChinaGrant/Award Number:2019YFA0801601+1 种基金National Natural Science Foundation of ChinaGrant/Award Number:31930029,91854111 and 31571490。
文摘The G-quadruplex(G4)sequences are short fragments of 4-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences are usually folded into secondary“knot”structure via Hoogsteen hydrogen bond to exert negative regulation on a variety of biological processes,including DNA replication and transcription,mRNA translation,and telomere maintenance.Recent structural biological and mouse genetics studies have demonstrated that RHAU(DHX36)can bind and unwind the G4“knots”to modulate embryonic development and postnatal organ function.Deficiency of RHAU gives rise to embryonic lethality,impaired organogenesis,and organ dysfunction.These studies uncovered the pivotal G4 resolvase function of RHAU to release the G4 barrier,which plays fundamental roles in development and physiological homeostasis.This review discusses the latest advancements and findings in deciphering RHAU functions using animal models.
基金supported by the National Natural Science Foundation of China(grant nos.22034004 and 22027807)the National Key Research and Development Program of China(grant no.2021YFA1200104)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDB36000000)the Vanke Special Fund for Public Health and Health Discipline Development(grant no.2022Z82WKJ003).
文摘Genomic surveillance of monkeypox virus(MPXV)is essential to explore the reason of its unusual outbreak.Current phylogenomic analysis of the MPXV genome mainly focuses on the effect of amino acid mutations.Herein,we explore the evolutionary variation of RNA G-quadruplex(RG4)of MPXV and find that the genome evolution of MPXV can also produce new effects through changes in the RG4 structure.This RG4 is located in MPXV’s only Kelch-like C9L gene,which encodes for an antagonist of the innate immune response.The evolution of this virus increases the unfolding kinetic constant of C9L RG4 and promotes the C9 protein level in living cells.Importantly,all reported MPXV genomes in 2022 carry the C9L-RG4-5 pattern with the highest unfolding kinetic constant.Additionally,the RG4 ligand,RGB-1,can impede the unfolding of C9L-RG4-5 and thereby reduce the C9 protein level.These findings carve out a new path to comprehensively understanding MPXV virology.
