The MTNR1A mRNA is stabilized by the cytoplasmic hnRNPL in renal tubular cells

Yen Sung Huang, Kuo Cheng Lu, Hsu Wen Chao, Ann Chen, Tai Kuang Chao, Cheng Yi Guo, Hsin Yi Hsieh, Hsiu Ming Shih, Huey Kang Sytwu, Chia Chao Wu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)2023-2035
Number of pages13
JournalJournal of Cellular Physiology
Volume236
Issue number3
DOIs
Publication statusPublished - Mar 2021

Keywords

  • diurnal rhythm
  • heterogeneous nuclear ribonucleoprotein L
  • melatonin receptor 1A
  • membranous nephropathy
  • RNA stability

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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