BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Intron retention decreases METTL3 expression by inhibiting mRNA export to the cytoplasm

  • Sangsoo Lee (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
  • Haesoo Jung (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
  • Sunkyung Choi (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
  • Namjoon Cho (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
  • Eun-Mi Kim (Department of Predictive Toxicology, Korea Institute of Toxicology) ;
  • Kee Kwang Kim (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
  • 투고 : 2023.04.29
  • 심사 : 2023.06.20
  • 발행 : 2023.09.30
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초록

Methyltransferase-like 3 (METTL3), a key component of the m6A methyltransferase complex, regulates the splicing, nuclear transport, stability, and translation of its target genes. However, the mechanism underlying the regulation of METTL3 expression by alternative splicing (AS) remains unknown. We analyzed the expression pattern of METTL3 after AS in human tissues and confirmed the expression of an isoform retaining introns 8 and 9 (METTL3-IR). We confirmed the different intracellular localizations of METTL3-IR and METTL3 proteins using immunofluorescence microscopy. Furthermore, the endogenous expression of METTL3-IR at the protein level was different from that at the mRNA level. We found that 3'-UTR generation by intron retention (IR) inhibited the export of METTL3-IR mRNA to the cytoplasm, which in turn suppressed protein expression. To the best of our knowledge, this is the first study to confirm the regulation of METTL3 gene expression by AS, providing evidence that the suppression of METTL3 protein expression by IR is an integral part of the mechanism by which 3'-UTR generation regulates protein expression via inhibition of RNA export to the cytoplasm.

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과제정보

This work was supported by a National Research Foundation of Korea Grant [NRF-2022R1A2C1003870]; Korea Environment Industry & Technology Institute (KEITI) through the Environment Health Action Program, funded by Korea Ministry of Environment (MOE) [2022002960005].

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