Snurportin-1 maintains muscle niche integrity and myogenic progenitor homeostasis

Saracoglu, H. P.; Nashabat, M.; Kutlu, D. N.; Saribas, B.; Yilmaz, E.; Tur, S.; Kayserili, H.; Yaksi, E.; Nabavizadeh, N.; Escande-Beillard, N.

doi:10.64898/2026.09.24.749599

bioRxiv · 10.64898/2026.09.24.749599

Snurportin-1 maintains muscle niche integrity and myogenic progenitor homeostasis

Saracoglu, H. P.·Nashabat, M.·Kutlu, D. N.·Saribas, B.·Yilmaz, E.·Tur, S.·Kayserili, H.·Yaksi, E.·Nabavizadeh, N.·Escande-Beillard, N.

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Abstract

Loss-of-function variants in SNUPN, encoding the nuclear import factor Snurportin-1 (SPN1) required for spliceosomal small nuclear ribonucleoprotein (snRNP) transport, cause a recently described form of limb-girdle muscular dystrophy (LGMD). However, the role of SPN1 in skeletal muscle homeostasis remains poorly understood, in part due to the lack of a suitable in vivo model. Here, we generated a zebrafish snupn loss-of-function model that recapitulates key features of the skeletal muscle phenotype observed in patients. Mutant larvae developed severe locomotor impairment by 6 days post-fertilization (dpf), accompanied by sarcomeric disorganization and impaired muscle fiber integrity. Transcriptomic profiling at 6 dpf revealed widespread alternative splicing and transcriptional dysregulation, with prominent alterations in extracellular matrix and basement membrane components, together with upregulation of stress- and inflammation-associated genes. Notably, these late-stage abnormalities were preceded by disruption of the muscle progenitor population at 2 dpf, with reduced Pax7 progenitor abundance and myogenic gene expression together with altered muscle differentiation and organization. Together, these findings identify SPN1 as a key regulator of skeletal muscle homeostasis linking RNA processing to extracellular niche integrity and myogenic progenitor maintenance. This zebrafish model provides an in vivo platform for dissecting LGMD-associated disease mechanisms and developing therapeutic strategies aimed at restoring muscle function and regenerative capacity.

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Saracoglu, H. P., Nashabat, M., Kutlu, D. N., Saribas, B., Yilmaz, E., Tur, S., Kayserili, H., Yaksi, E., Nabavizadeh, N., Escande-Beillard, N.. 2026-09-29. Snurportin-1 maintains muscle niche integrity and myogenic progenitor homeostasis. https://doi.org/10.64898/2026.09.24.749599

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