ArticleThe FEBS journal2026
Long-read sequencing-based atlas of tissue-specific expression of DNM1L transcript variants.
Article in The FEBS journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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