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LINC01503-MP is a Mitochondrial Microprotein That Promotes Cell Proliferation and Oxidative Metabolism.

Dewani, N.; Ruiz-Orera, J.; Popp, O.; Liang, N.; Sugawara, M.; Schulz, J. F.; Witte, F.; Sandmann, C.; Tsuji, T.; Blachut, S.; Katagiri, T.; Kondova, I.; Owada, S.; Yoshii, S.; Kataoka, H.; Kurtz, A.; Nakase, H.; van Heesch, S.; Mertins, P.; Hübner, N.; Kanda, M.

2025-03-19 molecular biology
10.1101/2025.03.19.644091 bioRxiv
Show abstract

Long non-coding RNAs (lncRNAs) are well-established as key regulators of gene expression. However, emerging evidence reveals that some lncRNAs can also encode functional microproteins. In this study, we report the identification of an evolutionarily young microprotein encoded by LINC01503, expressed across several human tissues. This microprotein, designated as LINC01503-MP, localises to the mitochondria and exerts a proliferative effect on HCT116 colorectal cancer (CRC) cells. Functional studies reveal that LINC01503-MP regulates mitochondrial oxygen consumption rate, linking its activity to enhanced metabolic functions and cell proliferation. Interactome analyses identified multiple mitochondrial metabolism-related proteins as potential interaction partners. Our findings show that LINC01503-MP plays a role in the proliferative phenotype associated with LINC01503 upregulation in CRC, suggesting the functional significance of evolutionarily young, lncRNA-derived microproteins in cancer progression.

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