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Abstract U12-type or minor introns are found in most multicellular eukaryotes and constitute ∼0.5% of all introns in species with a minor spliceosome. Although the biological significance for the evolutionary conservation of U12-type introns is debated, mutations disrupting U12 splicing cause developmental defects in both plants and animals. In human hematopoietic stem cells, U12 splicing defects disrupt proper differentiation of myeloid lineages and are associated with myelodysplastic syndrome, predisposing individuals to acute myeloid leukemia. Mutants in the maize ortholog of RNA binding motif protein 48 (RBM48) have aberrant U12-type intron splicing. Human RBM48 was recently purified biochemically as part of the minor spliceosome and shown to recognize the 5′ end of the U6atac snRNA. In this report, we use CRISPR/Cas9-mediated ablation of RBM48 in human K-562 cells to show the genetic function of RBM48. RNA-seq analysis comparing wild-type and mutant K-562 genotypes found that 48% of minor intron-containing genes have significant U12-type intron retention in RBM48 mutants. Comparing these results to maize rbm48 mutants defined a subset of minor intron-containing genes disrupted in both species. Mutations in the majority of these orthologous minor intron-containing genes have been reported to cause developmental defects in both plants and animals. Our results provide genetic evidence that the primary defect of human RBM48 mutants is aberrant U12-type intron splicing, while a comparison of human and maize RNA-seq data identifies candidate genes likely to mediate mutant phenotypes of U12-type splicing defects.
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This content will become publicly available on March 14, 2026
Enhanced packaging of U6 small nuclear RNA and splicing-related proteins into extracellular vesicles during HIV infection
U6 small nuclear RNA (U6 snRNA), a critical spliceosome component primarily found in the nucleus, plays a vital role in RNA splicing. Our previous study, using the simian immunodeficiency virus (SIV) macaque model, revealed an increase of U6 snRNA in plasma extracellular vesicles (EVs) in acute retroviral infection. Given the limited understanding of U6 snRNA dynamics across cells and EVs, particularly in SIV infection, this research explores U6 snRNA trafficking and its association with splicing proteins in the nucleus, cytoplasm, and EVs. We observed a redistribution of U6 snRNA from the nucleus to EVs post-infection, accompanied by distinct protein profile changes and alterations in nucleic acid metabolism and spliceosome pathways. In addition, U6 machinery proteins changed in cells and EVs in a contrasting manner. The redistribution of U6 and related proteins we observed could be part of a viral strategy to redirect host splicing machinery, suggesting that U6 may have regulatory roles and be part of retroviral infection signature.
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- Award ID(s):
- 2244127
- PAR ID:
- 10579285
- Publisher / Repository:
- Science
- Date Published:
- Journal Name:
- Science Advances
- Volume:
- 11
- Issue:
- 11
- ISSN:
- 2375-2548
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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