國家衛生研究院 NHRI:Item 3990099045/12807
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12807


    Title: The MTNR1A mRNA is stabilized by the cytoplasmic hnRNPL in renal tubular cells
    Authors: Huang, YS;Lu, KC;Chao, HW;Chen, A;Chao, TK;Guo, CY;Hsieh, HY;Shih, HM;Sytwu, HK;Wu, CC
    Contributors: Institute of Molecular and Genomic Medicine
    Abstract: The downregulation of melatonin receptor 1A (MTNR1A) is associated with a range of pathological conditions, including membranous nephropathy. Knowledge of the mechanism underlying MTNR1A expression has been limited to the transcriptional regulation level. Here, RNA interference screening in human kidney cells revealed that heterogeneous nuclear ribonucleoprotein L (hnRNPL) upregulated MTNR1A RNA post-transcriptionally. hnRNPL knockdown or overexpression led to increased or decreased levels of cyclic adenosine monophosphate-responsive element-binding protein phosphorylation, respectively. Molecular studies showed that cytoplasmic hnRNPL exerts a stabilizing effect on the MTNR1A transcript through CA-repeat elements in its coding region. Further studies revealed that the interaction between hnRNPL and MTNR1A serves to protect MNTR1A RNA degradation by the exosome component 10 protein. MTNR1A, but not hnRNPL, displays a diurnal rhythm in mouse kidneys. Enhanced levels of MTNR1A recorded at midnight correlated with robust binding activity between cytoplasmic hnRNPL and the MTNR1A transcript. Both hnRNPL and MTNR1A were decreased in the cytoplasm of tubular epithelial cells from experimental membranous nephropathy kidneys, supporting their clinical relevance. Collectively, our data identified cytoplasmic hnRNPL as a novel player in the upregulation of MTNR1A expression in renal tubular epithelial cells, and as a potential therapeutic target.
    Date: 2021-03
    Relation: Journal of Cellular Physiology. 2021 Mar;236(3):2023-2035.
    Link to: http://dx.doi.org/10.1002/jcp.29988
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0021-9541&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000553655500001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85088787387
    Appears in Collections:[Hsiu-Ming Shih] Periodical Articles

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