Dysregulated minor intron splicing in cancer

Pre‐mRNA splicing is now widely recognized as a cotranscriptional and post‐transcriptional mechanism essential for regulating gene expression and modifying gene product function. Mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are now considered among...

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Bibliographic Details
Published in:Cancer science 2022-09, Vol.113 (9), p.2934-2942
Main Authors: Nishimura, Koutarou, Yamazaki, Hiromi, Zang, Weijia, Inoue, Daichi
Format: Article
Language:English
Subjects:
Bone marrow
Cancer
Dendritic cells
Gene expression
Genes
Genomes
Introns
Kinases
LZTR1
minor introns
Mutation
Ontology
Proteins
Regulatory sequences
Review
Spliceosomes
splicing
Splicing factors
Tumors
U12 spliceosome
ZRSR2
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Summary:Pre‐mRNA splicing is now widely recognized as a cotranscriptional and post‐transcriptional mechanism essential for regulating gene expression and modifying gene product function. Mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are now considered among the most recurrent genetic abnormalities in patients with cancer, particularly hematologic malignancies. These include mutations in the major (U2‐type) and minor (U12‐type) spliceosomes, which remove >99% and ~0.35% of introns, respectively. Growing evidence indicates that aberrant splicing of evolutionarily conserved U12‐type minor introns plays a crucial role in cancer as the minor spliceosome component, ZRSR2, is subject to recurrent, leukemia‐associated mutations, and intronic mutations have been shown to disrupt the splicing of minor introns. Here, we review the importance of minor intron regulation, the molecular effects of the minor (U12‐type) spliceosomal mutations and cis‐regulatory regions, and the development of minor intron studies for better understanding of cancer biology.
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.15476