A tRNA-derived RNA Fragment Plays an Important Role in the Mechanism of Arsenite -induced Cellular Responses

Shengxuan Liu, Yu Chen, Yuping Ren, Jiehua Zhou, Junping Ren, Inhan Lee, Xiaoyong Bao

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    Chronic exposure to environmental heavy metals is a worldwide health concern. It is acknowledged to be an important cause of lower respiratory tract damage in children. However, the molecular mechanisms underlying the heavy metal-induced cellular stress/toxicity are not completely understood. Small non-coding RNAs (sncRNAs), such as microRNAs (miRNA) and more recently identified tRNA-derived RNA fragments (tRFs), are critical to the posttranscriptional control of genes. We used deep sequencing to investigate whether cellular sncRNA profiles are changed by environmental heavy metals. We found that the treatment of arsenite, an important groundwater heavy metal, leads to abundant production of tRFs, that are ~30 nucleotides (nts) long and most of which correspond to the 5′-end of mature tRNAs. It is unlikely for these tRFs to be random degradation by-products, as the type of induced tRFs is heavy metal-dependent. Three most inducible tRFs and their roles in arsenite-induced cellular responses were then investigated. We identified that p65, an important transcription factor belonging to NF-κB family and also a key factor controlling inflammatory gene expression, is a regulated target of a tRF derived from 5′-end of mature tRNA encoding AlaCGC (tRF5-AlaCGC). tRF5-AlaCGC activates p65, subsequently leading to enhanced secretion of IL-8 in arsenite response. In this study, we also identified that endonuclease Dicer and angiogenin temporally control the induction of tRF5-AlaCGC, providing an insight into the control of tRF biogenesis and subsequently the prevention of cellular damage.

    Original languageEnglish (US)
    Article number16838
    JournalScientific Reports
    Volume8
    Issue number1
    DOIs
    StatePublished - Dec 1 2018

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    Transfer RNA
    Heavy Metals
    RNA
    Small Untranslated RNA
    Transcription Factor RelA
    High-Throughput Nucleotide Sequencing
    Endonucleases
    Groundwater
    Environmental Exposure
    arsenite
    MicroRNAs
    Interleukin-8
    Respiratory System
    Nucleotides
    Gene Expression
    Genes

    ASJC Scopus subject areas

    • General

    Cite this

    A tRNA-derived RNA Fragment Plays an Important Role in the Mechanism of Arsenite -induced Cellular Responses. / Liu, Shengxuan; Chen, Yu; Ren, Yuping; Zhou, Jiehua; Ren, Junping; Lee, Inhan; Bao, Xiaoyong.

    In: Scientific Reports, Vol. 8, No. 1, 16838, 01.12.2018.

    Research output: Contribution to journalArticle

    Liu, Shengxuan ; Chen, Yu ; Ren, Yuping ; Zhou, Jiehua ; Ren, Junping ; Lee, Inhan ; Bao, Xiaoyong. / A tRNA-derived RNA Fragment Plays an Important Role in the Mechanism of Arsenite -induced Cellular Responses. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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    abstract = "Chronic exposure to environmental heavy metals is a worldwide health concern. It is acknowledged to be an important cause of lower respiratory tract damage in children. However, the molecular mechanisms underlying the heavy metal-induced cellular stress/toxicity are not completely understood. Small non-coding RNAs (sncRNAs), such as microRNAs (miRNA) and more recently identified tRNA-derived RNA fragments (tRFs), are critical to the posttranscriptional control of genes. We used deep sequencing to investigate whether cellular sncRNA profiles are changed by environmental heavy metals. We found that the treatment of arsenite, an important groundwater heavy metal, leads to abundant production of tRFs, that are ~30 nucleotides (nts) long and most of which correspond to the 5′-end of mature tRNAs. It is unlikely for these tRFs to be random degradation by-products, as the type of induced tRFs is heavy metal-dependent. Three most inducible tRFs and their roles in arsenite-induced cellular responses were then investigated. We identified that p65, an important transcription factor belonging to NF-κB family and also a key factor controlling inflammatory gene expression, is a regulated target of a tRF derived from 5′-end of mature tRNA encoding AlaCGC (tRF5-AlaCGC). tRF5-AlaCGC activates p65, subsequently leading to enhanced secretion of IL-8 in arsenite response. In this study, we also identified that endonuclease Dicer and angiogenin temporally control the induction of tRF5-AlaCGC, providing an insight into the control of tRF biogenesis and subsequently the prevention of cellular damage.",
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