Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intro...Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intron splicing and its role in maize kernel development.PPR21 is a typical P-type PPR protein targeted to mitochondria.The ppr21 mutants are arrested in embryogenesis and endosperm development,leading to embryo lethality.Null mutations of PPR21 reduce the splicing efficiency of nad2 intron 1,2,and 4 and impair the assembly and activity of mitochondrial complex I.Previous studies show that the P-type PPR protein EMP12 is required for the splicing of identical introns.However,our protein interaction analyses reveal that PPR21 does not interact with EMP12.Instead,both PPR21 and EMP12 interact with the small MutS-related(SMR)domain-containing PPR protein 1(PPR-SMR1)and the short P-type PPR protein 2(SPR2).PPR-SMR1 interacts with SPR2,and both proteins are required for the splicing of many introns in mitochondria,including nad2 intron 1,2,and 4.These results suggest that a PPR21-(PPR-SMR1/SPR2)-EMP12 complex is involved in the splicing of nad2 introns in maize mitochondria.展开更多
Linear mRNA vaccines are constrained by exonuclease susceptibility and instability,leading to compromised antigen expression.Circular RNA(circRNA) lacking canonical 5' and 3' untranslated regions demonstrates ...Linear mRNA vaccines are constrained by exonuclease susceptibility and instability,leading to compromised antigen expression.Circular RNA(circRNA) lacking canonical 5' and 3' untranslated regions demonstrates intrinsic exonuclease resistance.Current circularization strategies face three principal limitations:chemical methods produce non-native 2',5'-phosphodiester bonds;ribozyme-mediated approaches are restricted to RNA fragments shorter than 500 nucleotides;the Anabaena Group I intron system retains immunogenic exon sequences.In contrast,the self-splicing Group I intron ribozyme from Tetrahymena enables precisely controlled circularization through autonomous structural rearrangement,yielding exonfree constructs.Through optimized purification protocols,historical scalability challenges are systematically addressed.This Perspective establishes the mechanistic rationale and therapeutic superiority of this engineered RNA circularization platform.展开更多
Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is ...Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is lacking.Here,we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas(TCGA)project.We identify a total of 21,835 IPA events,almost half of which are ubiquitously expressed.We identify 2761 unique dynamically changed IPA events across cancer types.Furthermore,we observe 8855 non-redundant clinically relevant IPA events,which could potentially be used as prognostic indicators.Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response.Finally,we develop a user-friendly data portal,IPACancer Atlas(http://www.tingni-lab.com/Pancan_IPA),to search and explore IPAs in cancer.展开更多
Cadmium(Cd)has seriously affected the quality of traditional Chinese medicinal material Salvia miltiorrhiza in recent years,threatening human health.The physiological and metabolic profiles of S.miltiorrhiza in respon...Cadmium(Cd)has seriously affected the quality of traditional Chinese medicinal material Salvia miltiorrhiza in recent years,threatening human health.The physiological and metabolic profiles of S.miltiorrhiza in response to Cd stress have been revealed in previous studies.However,transcriptional and post-transcriptional regulation in response to different degrees of Cd(0,25,50,and 100 mg/kg)stress in S.miltiorrhiza remains unclear.Here,transcriptome atlas in S.miltiorrhiza under different degrees of Cd Stress was unveiled using RNA sequencing(RNA-seq).These results showed that the profiles of gene expression were different in the response to Cd treatment.Defense response-related biological processes were involved in differentially expressed genes(DEGs).In total,1966 genes were identified as transcription factors(TFs)with seven expressed trends.Retained intron(RI)was the major phenomenon.Targeted genes of intron splicing factors were identified via weighted gene co-expression network analysis(WGCNA).All of these indicated that transcriptional and post-transcriptional regulations were involved in response to Cd stress in S.miltiorrhiza.Our study will provide the most comprehensive resource for studying heavy metals in traditional Chinese medicine plants.展开更多
基金supported by the National Natural Science Foundation of China(32072126 and 32230075)the Shandong Provincial Natural Science Foundation(ZR2019MC005).
文摘Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intron splicing and its role in maize kernel development.PPR21 is a typical P-type PPR protein targeted to mitochondria.The ppr21 mutants are arrested in embryogenesis and endosperm development,leading to embryo lethality.Null mutations of PPR21 reduce the splicing efficiency of nad2 intron 1,2,and 4 and impair the assembly and activity of mitochondrial complex I.Previous studies show that the P-type PPR protein EMP12 is required for the splicing of identical introns.However,our protein interaction analyses reveal that PPR21 does not interact with EMP12.Instead,both PPR21 and EMP12 interact with the small MutS-related(SMR)domain-containing PPR protein 1(PPR-SMR1)and the short P-type PPR protein 2(SPR2).PPR-SMR1 interacts with SPR2,and both proteins are required for the splicing of many introns in mitochondria,including nad2 intron 1,2,and 4.These results suggest that a PPR21-(PPR-SMR1/SPR2)-EMP12 complex is involved in the splicing of nad2 introns in maize mitochondria.
基金supported by the National Key Research&Development Program of China(Nos.2021YFC2302400,2021YFA1201000,2023YFC2606004)the Fundamental Research Funds for the Central Universities(No.2022CX01013)。
文摘Linear mRNA vaccines are constrained by exonuclease susceptibility and instability,leading to compromised antigen expression.Circular RNA(circRNA) lacking canonical 5' and 3' untranslated regions demonstrates intrinsic exonuclease resistance.Current circularization strategies face three principal limitations:chemical methods produce non-native 2',5'-phosphodiester bonds;ribozyme-mediated approaches are restricted to RNA fragments shorter than 500 nucleotides;the Anabaena Group I intron system retains immunogenic exon sequences.In contrast,the self-splicing Group I intron ribozyme from Tetrahymena enables precisely controlled circularization through autonomous structural rearrangement,yielding exonfree constructs.Through optimized purification protocols,historical scalability challenges are systematically addressed.This Perspective establishes the mechanistic rationale and therapeutic superiority of this engineered RNA circularization platform.
基金This work was financially supported by the National Natural Science Foundation of China(92249302,32370592)the National Key Research and Development Program of China(2023YFC3603300,2021YFA0909300).
文摘Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is lacking.Here,we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas(TCGA)project.We identify a total of 21,835 IPA events,almost half of which are ubiquitously expressed.We identify 2761 unique dynamically changed IPA events across cancer types.Furthermore,we observe 8855 non-redundant clinically relevant IPA events,which could potentially be used as prognostic indicators.Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response.Finally,we develop a user-friendly data portal,IPACancer Atlas(http://www.tingni-lab.com/Pancan_IPA),to search and explore IPAs in cancer.
基金supported by Jiangxi Provincial Natural Science Foundation(20232BAB216119)Science and Technology Research Project of Jiangxi Provincial Department of Education(GJJ2200978)+1 种基金Jiangxi Provincial Health Commission S&T Plan(SKJP220227132)Jiangxi Provincial Administration of Traditional Chinese Medicine S&T Program(2022A392).
文摘Cadmium(Cd)has seriously affected the quality of traditional Chinese medicinal material Salvia miltiorrhiza in recent years,threatening human health.The physiological and metabolic profiles of S.miltiorrhiza in response to Cd stress have been revealed in previous studies.However,transcriptional and post-transcriptional regulation in response to different degrees of Cd(0,25,50,and 100 mg/kg)stress in S.miltiorrhiza remains unclear.Here,transcriptome atlas in S.miltiorrhiza under different degrees of Cd Stress was unveiled using RNA sequencing(RNA-seq).These results showed that the profiles of gene expression were different in the response to Cd treatment.Defense response-related biological processes were involved in differentially expressed genes(DEGs).In total,1966 genes were identified as transcription factors(TFs)with seven expressed trends.Retained intron(RI)was the major phenomenon.Targeted genes of intron splicing factors were identified via weighted gene co-expression network analysis(WGCNA).All of these indicated that transcriptional and post-transcriptional regulations were involved in response to Cd stress in S.miltiorrhiza.Our study will provide the most comprehensive resource for studying heavy metals in traditional Chinese medicine plants.