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bioRxiv · 10.64898/2026.01.05.697839

The non-coding facet of Pink1 mRNA regulates mitochondria homeostasis

Wu, X.·Liu, Y.·Ma, R.·Wang, H.·Fan, R.·Yang, W.·Li, X.·Xu, G.·Chen, H.·Hu, P.
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Abstract

Coding and non-coding RNAs have traditionally been viewed as functionally distinct entities. Here, we found that the down-regulation of Pink1 due to Tet2 knockout (KO) in muscle cells resulted in mitochondria dysfunction and muscle fatigue. Surprisingly, both Pink1 mRNA alone and untranslatable ATG-deficient Pink1 RNA were sufficient to rescue the mitochondria defects in Tet2 KO cells. PINK1 protein was fast degraded shortly after translation and dispensable for functions of Pink1 mRNA in muscle cells. Moreover, a portion of Pink1 mRNA was located in mitochondria and interacted directly with mitochondria inner membrane located protein YME1L1, promoting its proteolytic cleavage of Opa1, a master regulator of mitochondria fusion, to generate the mature protein form. These findings uncovered a bona fide non-coding role for a canonical mRNA, suggesting that translation independent functions could be present in mRNAs with coding potentials, blurring the conventional dichotomy between coding and non-coding RNAs.

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Wu, X., Liu, Y., Ma, R., Wang, H., Fan, R., Yang, W., Li, X., Xu, G., Chen, H., Hu, P.. 2026-01-06. The non-coding facet of Pink1 mRNA regulates mitochondria homeostasis. https://doi.org/10.64898/2026.01.05.697839

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