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      Action mechanisms and research methods of tRNA-derived small RNAs

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          Abstract

          tRNA-derived small RNAs (tsRNAs), including tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), are small regulatory RNAs processed from mature tRNAs or precursor tRNAs. tRFs and tiRNAs play biological roles through a variety of mechanisms by interacting with proteins or mRNA, inhibiting translation, and regulating gene expression, the cell cycle, and chromatin and epigenetic modifications. The establishment and application of research technologies are important in understanding the biological roles of tRFs and tiRNAs. To study the molecular mechanisms of tRFs and tiRNAs, researchers have used a variety of bioinformatics and molecular biology methods, such as microarray analysis, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR); Northern blotting; RNA sequencing (RNA-seq); cross-linking, ligation and sequencing of hybrids (CLASH); and photoactivatable-ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP). This paper summarizes the classification, action mechanisms, and roles of tRFs and tiRNAs in human diseases and the related signal transduction pathways, targeted therapies, databases, and research methods associated with them.

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          Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

          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. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.
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            Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells.

            MicroRNAs (miRNAs) are emerging as important, albeit poorly characterized, regulators of biological processes. Key to further elucidation of their roles is the generation of more complete lists of their numbers and expression changes in different cell states. Here, we report a new method for surveying the expression of small RNAs, including microRNAs, using Illumina sequencing technology. We also present a set of methods for annotating sequences deriving from known miRNAs, identifying variability in mature miRNA sequences, and identifying sequences belonging to previously unidentified miRNA genes. Application of this approach to RNA from human embryonic stem cells obtained before and after their differentiation into embryoid bodies revealed the sequences and expression levels of 334 known plus 104 novel miRNA genes. One hundred seventy-one known and 23 novel microRNA sequences exhibited significant expression differences between these two developmental states. Owing to the increased number of sequence reads, these libraries represent the deepest miRNA sampling to date, spanning nearly six orders of magnitude of expression. The predicted targets of those miRNAs enriched in either sample shared common features. Included among the high-ranked predicted gene targets are those implicated in differentiation, cell cycle control, programmed cell death, and transcriptional regulation.
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              The expanding world of small RNAs in plants.

              Plant genomes encode various small RNAs that function in distinct, yet overlapping, genetic and epigenetic silencing pathways. However, the abundance and diversity of small-RNA classes varies among plant species, suggesting coevolution between environmental adaptations and gene-silencing mechanisms. Biogenesis of small RNAs in plants is well understood, but we are just beginning to uncover their intricate regulation and activity. Here, we discuss the biogenesis of plant small RNAs, such as microRNAs, secondary siRNAs and heterochromatic siRNAs, and their diverse cellular and developmental functions, including in reproductive transitions, genomic imprinting and paramutation. We also discuss the diversification of small-RNA-directed silencing pathways through the expansion of RNA-dependent RNA polymerases, DICER proteins and ARGONAUTE proteins.
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                Author and article information

                Contributors
                guojunming@nbu.edu.cn
                Journal
                Signal Transduct Target Ther
                Signal Transduct Target Ther
                Signal Transduction and Targeted Therapy
                Nature Publishing Group UK (London )
                2095-9907
                2059-3635
                30 June 2020
                30 June 2020
                2020
                : 5
                : 109
                Affiliations
                [1 ]GRID grid.203507.3, ISNI 0000 0000 8950 5267, Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, , Medical School of Ningbo University, ; 315211 Ningbo, China
                [2 ]GRID grid.496809.a, ISNI 0000 0004 1760 1080, Ningbo College of Health Sciences, ; Ningbo, 315000 Zhejiang China
                Author information
                http://orcid.org/0000-0003-2026-1075
                Article
                217
                10.1038/s41392-020-00217-4
                7326991
                32606362
                27f3d5af-9d2b-4bdc-b26f-d3ed8b962e3f
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 April 2020
                : 7 June 2020
                : 13 June 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100011002, National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund);
                Award ID: 81974316
                Award Recipient :
                Funded by: the Scientific Innovation Team Project of Ningbo (no. 2017C110019), and the K.C. Wong Magna Fund in Ningbo University.
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2020

                non-coding rnas,molecular medicine
                non-coding rnas, molecular medicine

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