Long-read sequencing-based atlas of tissue-specific expression of DNM1L transcript variants
- Author(s)
- Yan, F; Jabbari, JS; Ling, NXL; Kong, AM; Truong, JQ; Maddock, ML; Rosdah, AA; Langendorf, CG; Zhang, L; Lees, JG; Bass-Stringer, S; Onda, DA; Pébay, A; Dottori, M; Loh, K; Holien, JK; Lal, S; Davidson, NM; Oakhill, JS; Lim, SY;
- Journal Title
- FEBS Journal
- Publication Type
- Apr 29
- Abstract
- Dynamin-related protein 1 (Drp1), encoded by DNM1L, is essential for mitochondrial fission, but its functional roles remain unclear due to isoform-specific effects from alternative splicing. Short-read RNA sequencing fails to resolve full-length isoforms involving distant exons, limiting our understanding. Here, we applied targeted long-read sequencing to profile full-length DNM1L transcripts in human left ventricle and induced pluripotent stem cell-derived cardiomyocytes, recovering all annotated isoforms with conserved expression patterns and isoforms 1-4 being the most abundant. Functional assays revealed that isoform abundance does not predict enzymatic activity. Extending this to six different mouse tissues, we identified distinct, tissue-enriched expression profiles. Functional rescue in Drp1-knockout mouse embryonic fibroblasts showed isoform-dependent differences in mitochondrial fission. Isoforms lacking the A-insert robustly rescued mitochondrial fission, with maximal activity observed for variants also lacking the B-insert (e.g. isoform b), consistent with a modulatory role of exon 3 in Drp1 activity. Our cross-species atlas integrates long-read transcriptomics with functional validation, revealing how isoform diversity underpins tissue-specific mitochondrial dynamics and physiological roles of Drp1.
- Publisher
- Wiley
- Keywords
- Dnm1l; Drp1; cardiomyocytes; isoforms; left ventricle; mitochondrial dynamics
- Research Division(s)
- Advanced Technology and Biology; Blood Cells and Blood Cancer
- PubMed ID
- 42053410
- Publisher's Version
- https://doi.org/10.1111/febs.70568
- Open Access at Publisher's Site
https://doi.org/10.1111/febs.70568- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-05-07 08:23:27
Last Modified: 2026-05-07 08:25:05