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Transfer RNA-derived fragments and tRNA halves: biogenesis, biological functions and their roles in diseases

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Abstract

The number of studies on non-coding RNAs has increased substantially in recent years owing to their importance in gene regulation. However, the biological functions of small RNAs from abundant species of housekeeping non-coding RNAs (rRNA, tRNA, etc.) remain a highly studied topic. tRNA-derived small RNAs (tsRNAs) refer to the specific cleavage of tRNAs by specific nucleases [e.g., Dicer and angiogenin (ANG)] in particular cells or tissues or under certain conditions such as stress and hypoxia. tsRNAs are a type of non-coding small RNA that are widely found in the prokaryotic and eukaryotic transcriptomes and are generated from mature tRNAs or precursor tRNAs at different sites. There are two main types of tsRNAs, tRNA-derived fragments (tRFs) and tRNA halves. tRFs are 14–30 nucleotides (nt) long and mainly consist of three subclasses: tRF-5, tRF-3, and tRF-1. tRNA halves, which are 31–40 nt long, are generated by specific cleavage in the anticodon loops of mature tRNAs. There are two types of tRNA halves, 5′-tRNA halves and 3′-tRNA halves. tsRNAs have multiple biological functions including acting as signaling molecules in stress responses and as regulators of gene expression. Additionally, they have been considered to be involved in RNA processing, cell proliferation, translation suppression, the modulation of DNA damage response, and neurodegeneration. More importantly, they are closely related to the occurrence of many human diseases such as tumors, infectious diseases, metabolic diseases, and neurological diseases. Moreover, tsRNAs have the potential to become new biomarkers for disease diagnosis. Continuous investigations will help us to understand their generation and regulatory mechanisms as well as the possible roles of tRFs and tRNA halves.

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Funding

This study was supported by grants from the Applied Research Project on Nonprofit Technology of Zhejiang Province (no. 2016C33177), the Scientific Innovation Team Project of Ningbo (no. 2017C110019), the National Natural Science Foundation of China (no. 81772279), and the K.C. Wong Magna Fund in Ningbo University.

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  1. Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China

    Yijing Shen, Linwen Zhu, Tianwen Li & Junming Guo

  2. Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University and Ningbo No. 1 Hospital, Ningbo, 315010, China

    Xiuchong Yu & Zhilong Yan

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  1. Yijing Shen
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Shen, Y., Yu, X., Zhu, L. et al. Transfer RNA-derived fragments and tRNA halves: biogenesis, biological functions and their roles in diseases. J Mol Med 96, 1167–1176 (2018). https://doi.org/10.1007/s00109-018-1693-y

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