转运核糖核酸(tRNA)衍生的小分子RNA(transfer-RNA derived small RNA,tsRNA)是近年来新发现的一类由成熟tRNA或其前体通过特殊的内切酶介导产生的非编码RNA。已有的研究揭示,tsRNA能够在转录及转录后水平上调控基因表达,能以表观遗传...转运核糖核酸(tRNA)衍生的小分子RNA(transfer-RNA derived small RNA,tsRNA)是近年来新发现的一类由成熟tRNA或其前体通过特殊的内切酶介导产生的非编码RNA。已有的研究揭示,tsRNA能够在转录及转录后水平上调控基因表达,能以表观遗传调控因子方式,在多种生物体的生理和病理过程中发挥重要作用,因此,其逐渐成为生物医学的研究热点而引起广泛关注。而且越来越多的证据显示,tsRNA通过对应激反应、细胞增殖与凋亡、神经发育、突触可塑性、神经炎症与免疫调节、表观遗传、RNA加工和蛋白质翻译调控等参与许多神经精神疾病的发生和发展过程。该文主要就tsRNA的生成和分类及其生物学功能,阐述tsRNA在神经发育和神经精神疾病中的作用和可能作用机制,从而进一步揭示tsRNA作为神经精神疾病可靠生物标志物和治疗靶点的潜力。展开更多
The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findin...The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findings,highlighting the role of mitochondrial dysfunction in the pathogenesis of T2DM.By examining the molecular mechanisms through which these tRNA variants contribute to disease progression,the study introduces new targets for therapeutic strategies.We discuss the broader implications of these results,emphasizing the importance of understanding mitochondrial genetics in addressing T2DM.展开更多
Transfer RNAs(tRNAs)adopt a stable L-shaped tertiary structure crucial for their involvement in protein translation.Among various divalent metal ions,magnesium ions play a pivotal role in preserving the tertiary struc...Transfer RNAs(tRNAs)adopt a stable L-shaped tertiary structure crucial for their involvement in protein translation.Among various divalent metal ions,magnesium ions play a pivotal role in preserving the tertiary structure of tRNA.However,the precise location of the Mg^(2+)binding pocket in human tRNA remains elusive.In this investigation,we identified the Mg^(2+)binding site within human tRNAGln using suppressor tRNA^(Gln).This variant of tRNA recognizes premature stop codons(specificlly UAG)and facilitates the expression of fll-length proteis.By mutating sites 8 and C72 in supprssr tRNAcl,we assessed the decoding efficiency of the resulting mutant suppressor tRNAs,which serves as a measure of tRNA's ability to decode genetic information.Our analysis revealed that the U8C mutant suppressor tRNA exhibited a significantly lower Mg^(2+)content compared to the C72U mutant.Furthermore,we observed a notable reduction in decoding efficiency in the U8-mutated suppressor tRNA,as evidenced by GFP fluorescence and Western blotting analysis.Conversely,mutations at the C72 site had a comparatively minor impact on decoding efficiency.These findings underscored the tight binding of Mg^(2+)to the U8 site of human tRNAGln,crucial for maintaining the stability of tRNA tertiary structure and translation efficacy.Additionally,our investigation delved into the influence of glutamine availability on tRNA decoding efficiency at the cellular level.The results indicated that both the concentration of amino acids and the codon context of TAG could modulate tRNA decoding efficiency.This study provided valuable insights into the structure and function of tRNA,laying the groundwork for further exploration in this field.展开更多
As the most prevalent post-transcriptional modification in transfer RNAs(tRNAs),methylation dynamically and reversibly regulates the biosynthesis and maturation of tRNAs,exerting direct impacts on the abundance and fu...As the most prevalent post-transcriptional modification in transfer RNAs(tRNAs),methylation dynamically and reversibly regulates the biosynthesis and maturation of tRNAs,exerting direct impacts on the abundance and functions of tRNAs responsible for the accurate translation of messenger RNAs(mRNAs).Consequently,aberrant tRNA methylation can potentially lead to the production of abnormally expressed proteins and the dysregulation of cellular homeostasis,underscoring the significance of tRNA methylation in tumorigenesis.Recent research has highlighted the aberrant expression of its catalytic regulators and proposed mechanisms through which tRNA methylation directly or indirectly influences tumor biological characteristics.This review provides a comprehensive summary of current research on tRNA methylation and its role in cellular function,aiming to deepen our understanding of the biological significance of tRNA methylation in tumorigenesis and to explore the potential of targeting tRNA methylation and tRNA-derived small RNAs(tsRNAs)for cancer therapy.展开更多
The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pa...The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pathogenicity,and autophagy of the rice blast fungus.In this study,we further revealed that PoElp3 functions via tRNA-mediated protein integrity.Phenotypic analyses revealed that overexpression of two of the tRNAs,tK(UUU)and tQ(UUG)could rescue the defects inΔPoelp3 strain.TMT-based proteomic and transcriptional analyses demonstrated that 386 proteins were down-regulated inΔPoelp3 strain compared with wild type strain Guy11,in a transcription-independent manner.Codon usage assays revealed an enrichment of Glutamine CAA-biased mRNA in the 386 proteins compared with the 70-15 genome.In addition to those reported previously,we also found that PoErp9,a sphingolipid C9-methyltransferase,was down-regulated in theΔPoelp3strain.Through an ILV2-specific integration of PoERP9-GFP into the wild type andΔPoelp3 strain,we were able to show that PoErp9 was positively regulated by PoElp3 translationally but not transcriptionally.Functional analyses revealed that PoErp9 was involved in the fungal growth,conidial development,pathogenicity,and TORrelated autophagy homeostasis in Pyricularia oryzae.Taken together,our results suggested that PoElp3 acts through the tRNA-mediated translational efficiency to regulate asexual development,pathogenicity,sphingolipid metabolism,and autophagy in the rice blast fungus.展开更多
文摘转运核糖核酸(tRNA)衍生的小分子RNA(transfer-RNA derived small RNA,tsRNA)是近年来新发现的一类由成熟tRNA或其前体通过特殊的内切酶介导产生的非编码RNA。已有的研究揭示,tsRNA能够在转录及转录后水平上调控基因表达,能以表观遗传调控因子方式,在多种生物体的生理和病理过程中发挥重要作用,因此,其逐渐成为生物医学的研究热点而引起广泛关注。而且越来越多的证据显示,tsRNA通过对应激反应、细胞增殖与凋亡、神经发育、突触可塑性、神经炎症与免疫调节、表观遗传、RNA加工和蛋白质翻译调控等参与许多神经精神疾病的发生和发展过程。该文主要就tsRNA的生成和分类及其生物学功能,阐述tsRNA在神经发育和神经精神疾病中的作用和可能作用机制,从而进一步揭示tsRNA作为神经精神疾病可靠生物标志物和治疗靶点的潜力。
文摘The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findings,highlighting the role of mitochondrial dysfunction in the pathogenesis of T2DM.By examining the molecular mechanisms through which these tRNA variants contribute to disease progression,the study introduces new targets for therapeutic strategies.We discuss the broader implications of these results,emphasizing the importance of understanding mitochondrial genetics in addressing T2DM.
基金National Natural Science Foundation of China(Grant No.U23A20106)National Key Research and Development Program of China(Grant No.91510100MA6CG8UJ4K)。
文摘Transfer RNAs(tRNAs)adopt a stable L-shaped tertiary structure crucial for their involvement in protein translation.Among various divalent metal ions,magnesium ions play a pivotal role in preserving the tertiary structure of tRNA.However,the precise location of the Mg^(2+)binding pocket in human tRNA remains elusive.In this investigation,we identified the Mg^(2+)binding site within human tRNAGln using suppressor tRNA^(Gln).This variant of tRNA recognizes premature stop codons(specificlly UAG)and facilitates the expression of fll-length proteis.By mutating sites 8 and C72 in supprssr tRNAcl,we assessed the decoding efficiency of the resulting mutant suppressor tRNAs,which serves as a measure of tRNA's ability to decode genetic information.Our analysis revealed that the U8C mutant suppressor tRNA exhibited a significantly lower Mg^(2+)content compared to the C72U mutant.Furthermore,we observed a notable reduction in decoding efficiency in the U8-mutated suppressor tRNA,as evidenced by GFP fluorescence and Western blotting analysis.Conversely,mutations at the C72 site had a comparatively minor impact on decoding efficiency.These findings underscored the tight binding of Mg^(2+)to the U8 site of human tRNAGln,crucial for maintaining the stability of tRNA tertiary structure and translation efficacy.Additionally,our investigation delved into the influence of glutamine availability on tRNA decoding efficiency at the cellular level.The results indicated that both the concentration of amino acids and the codon context of TAG could modulate tRNA decoding efficiency.This study provided valuable insights into the structure and function of tRNA,laying the groundwork for further exploration in this field.
基金supported by grants from the National Natural Science Foundation of China(82273174 and 82072374)the Key Research and Development Program of Hunan Province(2023DK2001,2023SK2004,and 2023ZK1122).
文摘As the most prevalent post-transcriptional modification in transfer RNAs(tRNAs),methylation dynamically and reversibly regulates the biosynthesis and maturation of tRNAs,exerting direct impacts on the abundance and functions of tRNAs responsible for the accurate translation of messenger RNAs(mRNAs).Consequently,aberrant tRNA methylation can potentially lead to the production of abnormally expressed proteins and the dysregulation of cellular homeostasis,underscoring the significance of tRNA methylation in tumorigenesis.Recent research has highlighted the aberrant expression of its catalytic regulators and proposed mechanisms through which tRNA methylation directly or indirectly influences tumor biological characteristics.This review provides a comprehensive summary of current research on tRNA methylation and its role in cellular function,aiming to deepen our understanding of the biological significance of tRNA methylation in tumorigenesis and to explore the potential of targeting tRNA methylation and tRNA-derived small RNAs(tsRNAs)for cancer therapy.
基金supported by National Natural Science Foundation of China(32172365 and 32272513)the Central Guidance on Local Science and Technology Development Fund of Fujian Province,China(2022L3088)the Innovative Research Funding of Fujian Agriculture and Forestry University,China(CXZX2020153D)。
文摘The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pathogenicity,and autophagy of the rice blast fungus.In this study,we further revealed that PoElp3 functions via tRNA-mediated protein integrity.Phenotypic analyses revealed that overexpression of two of the tRNAs,tK(UUU)and tQ(UUG)could rescue the defects inΔPoelp3 strain.TMT-based proteomic and transcriptional analyses demonstrated that 386 proteins were down-regulated inΔPoelp3 strain compared with wild type strain Guy11,in a transcription-independent manner.Codon usage assays revealed an enrichment of Glutamine CAA-biased mRNA in the 386 proteins compared with the 70-15 genome.In addition to those reported previously,we also found that PoErp9,a sphingolipid C9-methyltransferase,was down-regulated in theΔPoelp3strain.Through an ILV2-specific integration of PoERP9-GFP into the wild type andΔPoelp3 strain,we were able to show that PoErp9 was positively regulated by PoElp3 translationally but not transcriptionally.Functional analyses revealed that PoErp9 was involved in the fungal growth,conidial development,pathogenicity,and TORrelated autophagy homeostasis in Pyricularia oryzae.Taken together,our results suggested that PoElp3 acts through the tRNA-mediated translational efficiency to regulate asexual development,pathogenicity,sphingolipid metabolism,and autophagy in the rice blast fungus.
