Transfer RNA-derived small RNAs in the cancer transcriptome

Green, Darrell, Fraser, William and Dalmay, Tamas (2016) Transfer RNA-derived small RNAs in the cancer transcriptome. Pflügers Archiv European Journal of Physiology, 468 (6). 1041–1047. ISSN 0031-6768

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    Abstract

    The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing.

    Item Type: Article
    Additional Information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
    Uncontrolled Keywords: non-coding rna,trna,small rna,rna silencing,cancer
    Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
    Faculty of Science
    Faculty of Science > School of Biological Sciences
    Depositing User: Pure Connector
    Date Deposited: 29 Apr 2016 17:00
    Last Modified: 09 Apr 2019 11:11
    URI: https://ueaeprints.uea.ac.uk/id/eprint/58509
    DOI: 10.1007/s00424-016-1822-9

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