Many biological functions of RNA molecules are re- lated to their pseudoknot structures. It is significant for predicting the structure and function of RNA that learning about the stability and the process of RNA pseu...Many biological functions of RNA molecules are re- lated to their pseudoknot structures. It is significant for predicting the structure and function of RNA that learning about the stability and the process of RNA pseudoknot folding and unfolding. The structural features of mouse mammary tumor virus （MMTV） RNA pseudoknot in different ion concentration, the unfolding process of the RNA pseudoknot, and the two hairpin helices that constitute the RNA pseudoknot were studied with all atom molecule dynam- ics simulation method in this paper. We found that the higher cation concentration can cause structure of the RNA molecules more stable, and ions played an indispensable role in keeping the structure of RNA molecules stable; the unfolding process of hair- pin structure was corresponding to the antiprocess of its folding process. The main pathway of pseudoknot unfolding was that the inner base pair opened first, and then, the two helices, which formed the RNA pseudoknot opened decussately, while the folding pathway of the RNA pseudoknot was a helix folding after forma- tion of the other helix. Therefore, the unfolding process of RNA pseudoknot is different from the antiprocess of its folding process, and the unfolding process of each helix in the RNA pseudoknot is similar to the hairpin structure＇s unfolding process, which means that both are the unzipping process.展开更多
The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity.Here,we show that carrimycin,a new macrolide antibiotic in the...The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity.Here,we show that carrimycin,a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials,decreases the efficiency of programmed–1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion.Carrimycin binds directly to the coronaviral frameshift-stimulatory element(FSE)RNA pseudoknot,interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes.Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses.Because the FSE mechanism is essential in all coronaviruses,carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA.This finding may open a new direction in antiviral drug discovery for coronavirus variants.展开更多
We present in this paper an ab initio method, named KnotFold, for RNA H-type pseudoknot prediction. Our method employs an ensemble of RNA folding tools and a filtering heuristic to generate a set of pseudoknot-free st...We present in this paper an ab initio method, named KnotFold, for RNA H-type pseudoknot prediction. Our method employs an ensemble of RNA folding tools and a filtering heuristic to generate a set of pseudoknot-free stems, and then predicts pseudoknots by utilizing a search technique with a pseudo-probability scoring scheme. Experimental results show that KnotFold achieves higher sensitivity than existing methods. The KnotFold package with documentation is freely available at http：//bioinformatics.njit.edu/KnotFold.展开更多
TMV(24A+UPD)is a mutant virus that a 24 nt internal poly(A)tract was introduced downstream of the coat protein(CP)gene in TMV genome.TMV(24A+UPD)induced more severe necrosis in Nicotiana benthamiana and its RNA level ...TMV(24A+UPD)is a mutant virus that a 24 nt internal poly(A)tract was introduced downstream of the coat protein(CP)gene in TMV genome.TMV(24A+UPD)induced more severe necrosis in Nicotiana benthamiana and its RNA level accumulated at higher level than that of TMV,indicating that the introduced 24 nt poly(A)tract enhanced virus replication and virulence.In this study,TMV(24A+UPD)was serially passaged 10 times in N.benthamiana to analyze the predominant sequence changes of the introduced internal poly(A)tract and the upstream pseudoknot domain(UPD)in its genome.Results showed that the introduced 24 nt of the poly(A)tract was extended from first to seventh rounds of serial passaging,but shortened from the eighth passage,and reduced to only three adenines at the tenth passage.Also,the nucleotide sequences downstream of the introduced poly(A)tract were deleted gradually during the 10 cycles of passaging.There were mutant viruses generated with partial deletion of CP gene during serial passaging,indicating that extension of the introduced internal poly(A)tract also led to deletion of coding gene sequence of TMV(24A+UPD).These results provided valuable information for our understanding of the dynamics in viral sequence changes to reach a tipping point in its host plants in order to maintain a co-existence relationship during virus evolution.In addition,the introduction of an internal poly(A)tract may be applied to other viruses to study virus evolution and natural selection in host plants.展开更多
RNA二级结构预测是计算分子生物学中的一个重要领域.本文介绍了RNA二级结构的预测方法,包括该问题的数学模型、主要算法思想以及每种算法对应的软件.在tRNA和RNase P RNA数据库中随机选取了几组样例对目前主要的7种软件进行测试,同时对...RNA二级结构预测是计算分子生物学中的一个重要领域.本文介绍了RNA二级结构的预测方法,包括该问题的数学模型、主要算法思想以及每种算法对应的软件.在tRNA和RNase P RNA数据库中随机选取了几组样例对目前主要的7种软件进行测试,同时对每种软件的优缺点进行了详细比较.实验证明,当存在同源序列时,Pfold的效果优于其它软件.最后,在总结分析现有算法的基础上探讨了该领域进一步的研究方向.展开更多
基金Supported by the National Natural Science Foundation of China(10774115)the Doctoral Fund of Ministry of Education of China(20110141110009)
文摘Many biological functions of RNA molecules are re- lated to their pseudoknot structures. It is significant for predicting the structure and function of RNA that learning about the stability and the process of RNA pseudoknot folding and unfolding. The structural features of mouse mammary tumor virus （MMTV） RNA pseudoknot in different ion concentration, the unfolding process of the RNA pseudoknot, and the two hairpin helices that constitute the RNA pseudoknot were studied with all atom molecule dynam- ics simulation method in this paper. We found that the higher cation concentration can cause structure of the RNA molecules more stable, and ions played an indispensable role in keeping the structure of RNA molecules stable; the unfolding process of hair- pin structure was corresponding to the antiprocess of its folding process. The main pathway of pseudoknot unfolding was that the inner base pair opened first, and then, the two helices, which formed the RNA pseudoknot opened decussately, while the folding pathway of the RNA pseudoknot was a helix folding after forma- tion of the other helix. Therefore, the unfolding process of RNA pseudoknot is different from the antiprocess of its folding process, and the unfolding process of each helix in the RNA pseudoknot is similar to the hairpin structure＇s unfolding process, which means that both are the unzipping process.
基金supported by grants from the National Natural Science Foundation,China(82151525)the National key research and development program,China(2022YFC0869000)the CAMS Innovation Fund for Medical Sciences(2022-I2M-JB-013,2021-I2M-1-028 and 2022-I2M-2-002,China).
文摘The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity.Here,we show that carrimycin,a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials,decreases the efficiency of programmed–1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion.Carrimycin binds directly to the coronaviral frameshift-stimulatory element(FSE)RNA pseudoknot,interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes.Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses.Because the FSE mechanism is essential in all coronaviruses,carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA.This finding may open a new direction in antiviral drug discovery for coronavirus variants.
文摘We present in this paper an ab initio method, named KnotFold, for RNA H-type pseudoknot prediction. Our method employs an ensemble of RNA folding tools and a filtering heuristic to generate a set of pseudoknot-free stems, and then predicts pseudoknots by utilizing a search technique with a pseudo-probability scoring scheme. Experimental results show that KnotFold achieves higher sensitivity than existing methods. The KnotFold package with documentation is freely available at http：//bioinformatics.njit.edu/KnotFold.
基金Singapore Ministry of Education Tier 1 Academic Research grant R-154-000-B23–114 through National University of Singapore,Suzhou Science&Technology Bureau grant SNG2018039National Natural Science Foundation of China grant 31872639.
文摘TMV(24A+UPD)is a mutant virus that a 24 nt internal poly(A)tract was introduced downstream of the coat protein(CP)gene in TMV genome.TMV(24A+UPD)induced more severe necrosis in Nicotiana benthamiana and its RNA level accumulated at higher level than that of TMV,indicating that the introduced 24 nt poly(A)tract enhanced virus replication and virulence.In this study,TMV(24A+UPD)was serially passaged 10 times in N.benthamiana to analyze the predominant sequence changes of the introduced internal poly(A)tract and the upstream pseudoknot domain(UPD)in its genome.Results showed that the introduced 24 nt of the poly(A)tract was extended from first to seventh rounds of serial passaging,but shortened from the eighth passage,and reduced to only three adenines at the tenth passage.Also,the nucleotide sequences downstream of the introduced poly(A)tract were deleted gradually during the 10 cycles of passaging.There were mutant viruses generated with partial deletion of CP gene during serial passaging,indicating that extension of the introduced internal poly(A)tract also led to deletion of coding gene sequence of TMV(24A+UPD).These results provided valuable information for our understanding of the dynamics in viral sequence changes to reach a tipping point in its host plants in order to maintain a co-existence relationship during virus evolution.In addition,the introduction of an internal poly(A)tract may be applied to other viruses to study virus evolution and natural selection in host plants.
文摘RNA二级结构预测是计算分子生物学中的一个重要领域.本文介绍了RNA二级结构的预测方法,包括该问题的数学模型、主要算法思想以及每种算法对应的软件.在tRNA和RNase P RNA数据库中随机选取了几组样例对目前主要的7种软件进行测试,同时对每种软件的优缺点进行了详细比较.实验证明,当存在同源序列时,Pfold的效果优于其它软件.最后,在总结分析现有算法的基础上探讨了该领域进一步的研究方向.
