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1.
Ribosome-associated noncoding (ranc) RNAs are a novel class of short regulatory RNAs with functions and origins that have not been well studied. In this present study, we functionally characterized the molecular activity of Saccharomyces cerevisiae transfer RNA (tRNA)-derived fragments (tRFs) during protein biosynthesis. Our results indicate ribosome-associated tRFs derived from both 5′ (ranc-5′-tRFs) and 3′-part of tRNAs (ranc-3′-tRFs) have regulatory roles during translation. We demonstrated five 3′-tRFs and one 5′-tRF associate with a small ribosomal subunit and aminoacyl-tRNA synthetases (aa-RSs) in yeast. Furthermore, we discovered that four yeast aa-RSs interact directly with yeast ribosomes. tRFs interactions with ribosome-associated aa-RSs correlate with impaired efficiency of tRNA aminoacylation.  相似文献   

2.
tRNA主要功能是转运氨基酸参与蛋白质合成,在蛋白质生物合成过程中起着关键性的作用.近年来发现,tRNA是细胞内小RNA分子的重要来源,具有其它重要的生物学功能.来源于成熟tRNA分子的tRNA片段根据切割位置及生成机制的不同,主要分为两类:一类是tRNA半分子(tRNA halves);另一类是较小的tRNA片段,称为tRFs( tRNA fragments).在哺乳动物细胞中,tRNA半分子由血管生成素在tRNA分子反密码环处切割生成.本文主要针对tRNA半分子的加工机制、功能及在临床上的潜在应用进行综述.  相似文献   

3.
tRFs(tRNA-derived RNA fragments)是来源于tRNA的小分子非编码RNA,由前体tRNA或成熟tRNA经加工和修饰而成,在生物界中广泛存在。tRFs深度测序结果表明,tRFs可能并不是由tRNA随机裂解产生的,而是通过某个特定机制生成。根据来源不同,tRFs可被分为tRF-1、tRF-2、tRF-3、tRF-5和tiR。tRFs具有类似于miRNA的调控功能,并能参与调控基因转录和翻译,细胞增殖以及细胞应激反应。新近研究表明,乳腺癌细胞中某些特异性的tRFs(如tRFGlyTCC和tRFAspGTC),可通过与Y-box结合蛋白1(Y box binding protein 1, YB-1)结合进而抑制癌细胞的生长和转移。另有研究表明,tRFs还可通过细胞色素c介导的信号转导途径来发挥其抑制癌细胞凋亡的功能。由此可见,tRFs在调控癌症发生发展过程中也具有重要调控作用,然而其机制仍不清楚。本文综述了tRFs结构和分布、生物学功能及其作用机制的研究现状,旨在为tRFs相关研究提供参考。  相似文献   

4.
The fundamental biological roles of a class of small noncoding RNAs (sncRNAs), derived from mature tRNAs or pre-tRNAs, in human diseases have received increasing attention in recent years. These ncRNAs are called tRNA-derived fragments (tRFs) or tRNA-derived small RNAs (tsRNAs). tRFs mainly include tRF-1, tRF-5, tRF-3 and tRNA halves (tiRNAs or tRHs), which are produced by enzyme-specific cleavage of tRNAs. Here, we classify tRF-5 and 5′ tiRNAs into the same category: 5′-tRFs and review the biological functions and regulatory mechanisms of 5′-tRFs in cancer and other diseases (metabolic diseases, neurodegenerative diseases, pathological stress injury and virus infection) to provide a new theoretical basis for the diagnosis and treatment of diseases.  相似文献   

5.
转移核糖核酸(tRNA)是蛋白质合成的关键接头分子,特异性识别信使RNA(mRNA)的密码子信息,将其接载的氨基酸基团掺入到新生多肽链中。最新研究表明,在很多物种中,在某些特定情况下,tRNA或其前体被特异性剪切产生tRNA来源的小片段RNA(tRNA-derived fragment,tRF)。这类tRF是一类新的基因表达调控因子,其发挥作用的机制多样,如某些tRF以microRNA方式抑制mRNA翻译;某些tRF作为逆转录病毒RNA基因组的逆转录引物;而某些tRF参与了前体rRNA剪切复合物的组装。此外,细胞受胁迫产生的带有多聚鸟苷酸模块的tRF则会竞争性抑制延伸因子elF4G与mRNA的结合,从而抑制蛋白质翻译。随着研究的继续深入,对tRF的发生发展、作用机制以及在疾病中的潜在作用将会进一步丰富。拟从tRF作为新的基因表达调控分子的角度,简要介绍tRF发挥作用的分子机制。  相似文献   

6.
近年来,转运RNA(transfer RNA,tRNA)衍生的小RNA(tRNA-derived small RNA,tsRNAs)被认为是一种新的、潜在的非编码RNAs(non-coding RNA,ncRNAs)。根据在前体或成熟tRNA上切割位置的不同,tsRNAs主要被分为两种类型,即tRNA halves(tRNA-derived stress-induced RNA,tiRNAs)和tRNA衍生片段(tRNA-derived fragment,tRFs)。越来越多的证据表明,tsRNAs参与翻译起始抑制、基因沉默和调节核糖体发生等多种细胞代谢过程,并在癌症、神经退行性疾病、代谢性疾病和病毒感染等相关疾病的发生、发展中都起着重要的作用。综述tsRNAs生物学功能和作用机制及其在相关疾病中的潜在应用,总结tsRNAs研究目前存在的问题和未来的研究方向。  相似文献   

7.
8.
tRNA-derived small RNAs (tRFs), a kind of noncoding RNAs, are generated from transfer RNAs. tRFs have some types according to their source and sizes. They play important roles in cell life and carcinogenesis. In this paper, we review the biogenesis and biological properties. We also focus on current progress of tRFs and some tsRNAs such as tRF-Leu-CAG, which have been studied or will be further investigated in tumorgenesis and diagnostic biomarkers in the clinic.  相似文献   

9.
Recent evidences highlight the importance of mitochondria-nucleus communication for the clinical phenotype of oxidative phosphorylation (OXPHOS) diseases. However, the participation of small non-coding RNAs (sncRNAs) in this communication has been poorly explored. We asked whether OXPHOS dysfunction alters the production of a new class of sncRNAs, mitochondrial tRNA fragments (mt tRFs), and, if so, whether mt tRFs play a physiological role and their accumulation is controlled by the action of mt tRNA modification enzymes. To address these questions, we used a cybrid model of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), an OXPHOS disease mostly caused by mutation m.3243A>G in the mitochondrial tRNALeu(UUR) gene. High-throughput analysis of small-RNA-Seq data indicated that m.3243A>G significantly changed the expression pattern of mt tRFs. A functional analysis of potential mt tRFs targets (performed under the assumption that these tRFs act as miRNAs) indicated an association with processes that involve the most common affected tissues in MELAS. We present evidences that mt tRFs may be biologically relevant, as one of them (mt i-tRF GluUUC), likely produced by the action of the nuclease Dicer and whose levels are Ago2 dependent, down-regulates the expression of mitochondrial pyruvate carrier 1 (MPC1), promoting the build-up of extracellular lactate. Therefore, our study underpins the idea that retrograde signaling from mitochondria is also mediated by mt tRFs. Finally, we show that accumulation of mt i-tRF GluUUC depends on the modification status of mt tRNAs, which is regulated by the action of stress-responsive miRNAs on mt tRNA modification enzymes.  相似文献   

10.
11.
《FEBS letters》2014,588(23):4297-4304
Transfer RNA (tRNA) is traditionally considered to be an adaptor molecule that helps ribosomes to decode messenger RNA (mRNA) and synthesize protein. Recent studies have demonstrated that tRNAs also serve as a major source of small non-coding RNAs that possess distinct and varied functions. These tRNA fragments are heterogeneous in size, nucleotide composition, biogenesis and function. Here we describe multiple roles that tRNA fragments play in cell physiology and discuss their relevance to human health and disease.  相似文献   

12.
13.
刘魏  童永鳌  白洁 《植物学报》2018,53(5):625-633
tRNA片段(tRF)是tRNA通过非随机剪切产生的RNA片段, 其产生和功能机制尚不明确; 而在水稻(Oryza sativa)雄配子体发育过程中, 人们对tRNA更是知之甚少。通过高通量测序, 在水稻雄配子体发育过程中发现了长度范围较大的tRFs; 进一步采用logo对tRFs两端的序列进行分析, 发现了4个有序列特征(其中3个未见报道)和1个无序列特征的酶切位点; 通过NCBI Blast预测了tRF靶基因, 发现其大多靶向转座因子。研究结果对揭示tRF产生机制以及水稻雄配子体发育研究有一定的参考价值。  相似文献   

14.
15.
The folding of tRNA fragments (tRFs) into G-quadruplex structures and the implications of G-quadruplexes in translational inhibition have been studied mainly in mammalian systems. To increase our knowledge of these phenomena, we determined the influence of human and plant tRFs and model G-quadruplexes on translation in rabbit reticulocyte lysate and wheat germ extract. The efficiency of translational inhibition in the mammalian system was strongly associated with the type of G-quadruplex topology. In the plant system, the ability of a small RNA to adopt the G-quadruplex conformation was not sufficient to repress translation, indicating the importance of other structural determinants.  相似文献   

16.
Small non-coding RNAs (sncRNAs) are indispensable for proper germ cell development, emphasizing the need for greater elucidation of the mechanisms of germline development and regulation of this process by sncRNAs. We used deep sequencing to characterize three families of small non-coding RNAs (piRNAs, miRNAs, and tRFs) present in Sus scrofa gonads and focused on the small RNA fraction present in both male and female gonads. Although similar numbers of reads were obtained from both types of gonads, the number of unique RNA sequences in the ovaries was several times lower. Of the sequences detected in the testes, 2.6% of piRNAs, 9% of miRNAs, and 10% of tRFs were also present in the ovaries. Notably, the majority of the shared piRNAs mapped to ribosomal RNAs and were derived from clustered loci. In addition, the most abundant miRNAs present in the ovaries and testes are conserved and are involved in many biological processes such as the regulation of homeobox genes, the control of cell proliferation, and carcinogenesis. Unexpectedly, we detected a novel sncRNA type, the tRFs, which are 30–36-nt RNA fragments derived from tRNA molecules, in gonads. Analysis of S. scrofa piRNAs show that testes specific piRNAs are biased for 5′ uracil but both testes and ovaries specific piRNAs are not biased for adenine at the 10th nucleotide position. These observations indicate that adult porcine piRNAs are predominantly produced by a primary processing pathway or other mechanisms and secondary piRNAs generated by ping-pong mechanism are absent.  相似文献   

17.
RNase T2 enzymes are produced by a wide range of organisms and have been implicated to function in diverse cellular processes, including stress-induced anticodon loop cleavage of mature tRNAs to generate tRNA halves. Here we describe a family of eight RNase T2 genes (RNT2A-RNT2H) in the ciliate Tetrahymena thermophila. We constructed strains lacking individual or combinations of these RNT2 genes that were viable but had distinct cellular and molecular phenotypes. In strains lacking only one Rnt2 protein or lacking a subfamily of three catalytically inactive Rnt2 proteins, starvation-induced tRNA fragments continued to accumulate, with only a minor change in fragment profile in one strain. We therefore generated strains lacking pairwise combinations of the top three candidates for Rnt2 tRNases. Each of these strains showed a distinct starvation-specific profile of tRNA and rRNA fragment accumulation. These results, the delineation of a broadened range of conditions that induce the accumulation of tRNA halves, and the demonstration of a predominantly ribonucleoprotein-free state of tRNA halves in cell extract suggest that ciliate tRNA halves are degradation intermediates in an autophagy pathway induced by growth arrest that functions to recycle idle protein synthesis machinery.  相似文献   

18.
19.
tRNA cleavage is a conserved response to oxidative stress in eukaryotes   总被引:4,自引:0,他引:4  
Recent results have identified a diversity of small RNAs in a wide range of organisms. In this work, we demonstrate that Saccharomyces cerevisiae contains a small RNA population consisting primarily of tRNA halves and rRNA fragments. Both 5′ and 3′ fragments of tRNAs are detectable by Northern blot analysis, suggesting a process of endonucleolytic cleavage. tRNA and rRNA fragment production in yeast is most pronounced during oxidative stress conditions, especially during entry into stationary phase. Similar tRNA fragments are also observed in human cell lines and in plants during oxidative stress. These results demonstrate that tRNA cleavage is a conserved aspect of the response to oxidative stress.  相似文献   

20.
Crick(1955)预见到细胞内存在一种小分子RNA称为"衔接子",并假定它是一种沟通DNA与蛋白质序列之间的中介体。Zamecnik(1955)发现sRNA(tRNA),Hoagland(1954)发现氨基酸激活酶(氨基酰-tRNA合成酶)。镁离子稳定tRNA的二级结构(1963),由此,可以得到大的寡核苷酸片断,甚至tRNA的半分子。这项技术大大推动了tRNA及其他RNA序列分析工作的迅速进展。Holley(1965)首次测定出酵母tRNAAla全部核苷酸序列,并设计出一种"三叶草"二级结构。Crick(1966)较早地提出"摆动假说",即反密码子5’端的碱基并不与密码子3’端碱基严格配对,允许有一定的摆动。Rich(1974)等用X射线晶体衍射法,阐明了酵母tRNAPhe的高级结构(呈L型)。2000年,英国剑桥科学家,使用在冰箱保存了15年的酵母tRNAPhe晶体,重新测定它的L型结构是正确的,并严格确定其中10个镁离子和一个精胺分子的精确部位。  相似文献   

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