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Siqi Li, Zhengping Xu, Jinghao Sheng
Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes...
May 10, 2018: Genes
X He, F Li, B Bor, K Koyano, L Cen, X Xiao, W Shi, D T W Wong
Coevolution of the human host and its associated microbiota has led to sophisticated interactions to maintain a delicate homeostasis. Emerging evidence suggests that in addition to small molecules, peptides, and proteins, small regulatory noncoding RNAs (sRNAs) might play an important role in cross-domain interactions. In this study, we revealed the presence of diverse host transfer RNA-derived small RNAs (tsRNAs) among human salivary sRNAs. We selected 2 tsRNAs (tsRNA-000794 and tsRNA-020498) for further study based on their high sequence similarity to specific tRNAs from a group of Gram-negative oral bacteria, including Fusobacterium nucleatum, a key oral commensal and opportunistic pathogen...
April 1, 2018: Journal of Dental Research
Shiqi Luo, Feng He, Junjie Luo, Shengqian Dou, Yirong Wang, Annan Guo, Jian Lu
Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of small RNAs, yet their regulatory roles have not been well understood. Here we studied the molecular mechanisms and consequences of tsRNA-mediated regulation in Drosophila. By analyzing 495 public small RNA libraries, we demonstrate that most tsRNAs are conserved, prevalent and abundant in Drosophila. By carrying out mRNA sequencing and ribosome profiling of S2 cells transfected with single-stranded tsRNA mimics and mocks, we show that tsRNAs recognize target mRNAs through conserved complementary sequence matching and suppress target genes by translational inhibition...
March 14, 2018: Nucleic Acids Research
Trees-Juen Chuang, Yen-Ju Chen, Chia-Ying Chen, Te-Lun Mai, Yi-Da Wang, Chung-Shu Yeh, Min-Yu Yang, Yu-Ting Hsiao, Tien-Hsien Chang, Tzu-Chien Kuo, Hsin-Hua Cho, Chia-Ning Shen, Hung-Chih Kuo, Mei-Yeh Lu, Yi-Hua Chen, Shan-Chi Hsieh, Tai-Wei Chiang
Transcriptionally non-co-linear (NCL) transcripts can originate from trans-splicing (trans-spliced RNA; 'tsRNA') or cis-backsplicing (circular RNA; 'circRNA'). While numerous circRNAs have been detected in various species, tsRNAs remain largely uninvestigated. Here, we utilize integrative transcriptome sequencing of poly(A)- and non-poly(A)-selected RNA-seq data from diverse human cell lines to distinguish between tsRNAs and circRNAs. We identified 24,498 NCL events and found that a considerable proportion (20-35%) of them arise from both tsRNAs and circRNAs, representing extensive alternative trans-splicing and cis-backsplicing in human cells...
January 27, 2018: Nucleic Acids Research
Hak Kyun Kim, Gabriele Fuchs, Shengchun Wang, Wei Wei, Yue Zhang, Hyesuk Park, Biswajoy Roy-Chaudhuri, Pan Li, Jianpeng Xu, Kirk Chu, Feijie Zhang, Mei-Sze Chua, Samuel So, Qiangfeng Cliff Zhang, Peter Sarnow, Mark A Kay
Transfer-RNA-derived small RNAs (tsRNAs; also called tRNA-derived fragments) are an abundant class of small non-coding RNAs whose biological roles are not well understood. Here we show that inhibition of a specific tsRNA, LeuCAG3'tsRNA, induces apoptosis in rapidly dividing cells in vitro and in a patient-derived orthotopic hepatocellular carcinoma model in mice. This tsRNA binds at least two ribosomal protein mRNAs (RPS28 and RPS15) to enhance their translation. A decrease in translation of RPS28 mRNA blocks pre-18S ribosomal RNA processing, resulting in a reduction in the number of 40S ribosomal subunits...
December 7, 2017: Nature
Veronica Balatti, Yuri Pekarsky, Carlo M Croce
Noncoding RNAs are untranslated RNA molecules that can be divided into two main types: infrastructural, including transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), and regulatory, including long ncRNAs (lncRNAs) and small ncRNAs (sRNA). Among small ncRNA, the role of microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) in cancer is well documented. Recently, other small ncRNAs have been described. In particular, tRNA-derived small RNAs (tsRNA) have been found to be frequently dysregulated in cancer. Since tsRNAs can be considered unique sequences and are able to bind both Argonaute proteins (like miRNAs) and Piwi proteins (like piRNAs), their dysregulation could play a critical role in cancer by interfering with gene expression regulation at different levels...
2017: Advances in Cancer Research
Veronica Balatti, Giovanni Nigita, Dario Veneziano, Alessandra Drusco, Gary S Stein, Terri L Messier, Nicholas H Farina, Jane B Lian, Luisa Tomasello, Chang-Gong Liu, Alexey Palamarchuk, Jonathan R Hart, Catherine Bell, Mariantonia Carosi, Edoardo Pescarmona, Letizia Perracchio, Maria Diodoro, Andrea Russo, Anna Antenucci, Paolo Visca, Antonio Ciardi, Curtis C Harris, Peter K Vogt, Yuri Pekarsky, Carlo M Croce
Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that the ts-4521/3676 cluster (now called " ts-101 " and " ts-53 ," respectively), ts-46 , and ts-47 are down-regulated in these malignancies...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
Rui Chen, Jian Du, Lin Ma, Li-Qing Wang, Sheng-Song Xie, Chang-Ming Yang, Xian-Yong Lan, Chuan-Ying Pan, Wu-Zi Dong
MicroRNAs (miRNAs) are 18-24 nucleotides non-coding RNAs that regulate gene expression by post-transcriptional suppression of mRNA. The Chinese giant salamander (CGS, Andrias davidianus), which is an endangered species, has become one of important models of animal evolution; however, no miRNA studies on this species have been conducted. In this study, two small RNA libraries of CGS ovary and testis were constructed using deep sequencing technology. A bioinformatics pipeline was developed to distinguish miRNA sequences from other classes of small RNAs represented in the sequencing data...
June 19, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
Yuri Pekarsky, Veronica Balatti, Alexey Palamarchuk, Lara Rizzotto, Dario Veneziano, Giovanni Nigita, Laura Z Rassenti, Harvey I Pass, Thomas J Kipps, Chang-Gong Liu, Carlo M Croce
Chronic lymphocytic leukemia (CLL) is the most common human leukemia, and transgenic mouse studies indicate that activation of the T-cell leukemia/lymphoma 1 (TCL1) oncogene is a contributing event in the pathogenesis of the aggressive form of this disease. While studying the regulation of TCL1 expression, we identified the microRNA cluster miR-4521/3676 and discovered that these two microRNAs are associated with tRNA sequences and that this region can produce two small RNAs, members of a recently identified class of small noncoding RNAs, tRNA-derived small RNAs (tsRNAs)...
May 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
Qi Chen, Menghong Yan, Zhonghong Cao, Xin Li, Yunfang Zhang, Junchao Shi, Gui-hai Feng, Hongying Peng, Xudong Zhang, Ying Zhang, Jingjing Qian, Enkui Duan, Qiwei Zhai, Qi Zhou
Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions...
January 22, 2016: Science
Maria R Garcia-Silva, Roberta Ferreira Cura das Neves, Florencia Cabrera-Cabrera, Julia Sanguinetti, Lia C Medeiros, Carlos Robello, Hugo Naya, Tamara Fernandez-Calero, Thais Souto-Padron, Wanderley de Souza, Alfonso Cayota
The protozoan parasite Trypanosoma cruzi has a complex life cycle characterized by intracellular and extracellular forms alternating between invertebrate and mammals. To cope with these changing environments, T. cruzi undergoes rapid changes in gene expression, which are achieved essentially at the posttranscriptional level. At present, expanding families of small RNAs are recognized as key players in novel forms of posttranscriptional gene regulation in most eukaryotes. However, T. cruzi lacks canonical small RNA pathways...
January 2014: Parasitology Research
Monir Shababi, Jacqueline Glascock, Christian L Lorson
Spinal muscular atrophy (SMA), a neurodegenerative disease, is the second most common genetic disorder and the leading genetic cause of infantile death. SMA arises from the loss of Survival Motor Neuron-1 (SMN1), leading to degeneration of lower motor neurons and, consequently, the atrophy of voluntary muscles. A duplicated copy gene called SMN2 exists in humans. SMN2 is unable to fully compensate for the loss of SMN1 because it produces very low levels of functional SMN protein due to an alternative splicing event...
February 2011: Human Gene Therapy
Dirk Haussecker, Yong Huang, Ashley Lau, Poornima Parameswaran, Andrew Z Fire, Mark A Kay
Competition between mammalian RNAi-related gene silencing pathways is well documented. It is therefore important to identify all classes of small RNAs to determine their relationship with RNAi and how they affect each other functionally. Here, we identify two types of 5'-phosphate, 3'-hydroxylated human tRNA-derived small RNAs (tsRNAs). tsRNAs differ from microRNAs in being essentially restricted to the cytoplasm and in associating with Argonaute proteins, but not MOV10. The first type belongs to a previously predicted Dicer-dependent class of small RNAs that we find can modestly down-regulate target genes in trans...
April 2010: RNA
Tristan H Coady, Travis D Baughan, Monir Shababi, Marco A Passini, Christian L Lorson
RNA modalities are developing as a powerful means to re-direct pathogenic pre-mRNA splicing events. Improving the efficiency of these molecules in vivo is critical as they move towards clinical applications. Spinal muscular atrophy (SMA) is caused by loss of SMN1. A nearly identical copy gene called SMN2 produces low levels of functional protein due to alternative splicing. We previously reported a trans-splicing RNA (tsRNA) that re-directed SMN2 splicing. Now we show that reducing the competition between endogenous splices sites enhanced the efficiency of trans-splicing...
2008: PloS One
V I Agol, S G Drozdov, M P Frolova, V P Grachev, M S Kolesnikova, V G Kozlov, N M Ralph, L I Romanova, E A Tolskaya, E G Viktorova
A tsRNA- intertypic recombinant, v3/a1-25, which has the 5' and 3' halves of the genome derived from the neurovirulent type 3 poliovirus strain 452/62 3D and the attenuated type 1 poliovirus strain LSc-gr3, respectively, was previously shown to cause severe paralytic poliomyelitis after intracerebral inoculation of monkeys. To ascertain whether the illness was caused by the recombinant itself or by temperature-resistant trRNA+ mutants that might have arisen in the inoculated monkeys, five independent virus strains have been isolated from the spinal cord of the diseased animals...
February 1985: Journal of General Virology
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