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Intron retention drives spliceosome reprogramming during osteogenic differentiation

ABSTRACT: The spliceosome, a complex of RNA and proteins, is indispensable for orchestrating splicing events critical to mRNA maturation. Mutations in spliceosome components are linked to tissue-specific diseases known as spliceosomopathies. Among the diverse splicing events mediated by the spliceosome, intron retention (IR) has been extensively studied in plants and fungi. However, its functional significance in mammals has only recently gained attention. IR is recognized for its role in the differentiation of neuronal and hematopoietic cells. This study leverages RNA sequencing to explore IR events during osteogenic differentiation in ST2 cells. Genome-wide analysis revealed a significant increase in IR during differentiation, affecting clusters of genes involved in RNA processing. The identification of premature termination codons (PTCs) within intron-retaining transcripts indicates that IR may regulate RNA processing gene expression through nonsense-mediated decay (NMD). Additionally, inhibition of NMD caused accumulation of these mRNA transcripts and disrupted osteogenic differentiation. We propose that IR triggers NMD to enhance mRNA decay in a fraction of splicing genes, leading to spliceosome reprogramming to facilitate osteogenic differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE310083 | GEO | 2026/08/23

REPOSITORIES: GEO

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Intron retention drives spliceosome reprogramming during osteogenic differentiation

Project description:Intron retention drives spliceosome reprogramming during osteogenic differentiation

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