Spliceosomopathies: Diseases and mechanisms

The spliceosome is a complex of RNA and proteins that function together to identify intron‐exon junctions in precursor messenger‐RNAs, splice out the introns, and join the flanking exons. Mutations in any one of the genes encoding the proteins that make up the spliceosome may result in diseases know...

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Bibliographic Details
Published in:Developmental dynamics 2020-09, Vol.249 (9), p.1038-1046
Main Authors: Griffin, Casey, Saint‐Jeannet, Jean‐Pierre
Format: Article
Language:English
Subjects:
Disorders
Dysostosis
Erythrocytes
Exons
Hemopoiesis
Introns
mandibulofacial dysostosis
Mutation
Myelodysplastic syndrome
Myelodysplastic syndromes
Phenotypes
Proteins
Retina
Retinitis
Retinitis pigmentosa
Ribonucleic acid
RNA
spliceosome
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Summary:The spliceosome is a complex of RNA and proteins that function together to identify intron‐exon junctions in precursor messenger‐RNAs, splice out the introns, and join the flanking exons. Mutations in any one of the genes encoding the proteins that make up the spliceosome may result in diseases known as spliceosomopathies. While the spliceosome is active in all cell types, with the majority of the proteins presumably expressed ubiquitously, spliceosomopathies tend to be tissue‐specific as a result of germ line or somatic mutations, with phenotypes affecting primarily the retina in retinitis pigmentosa, hematopoietic lineages in myelodysplastic syndromes, or the craniofacial skeleton in mandibulofacial dysostosis. Here we describe the major spliceosomopathies, review the proposed mechanisms underlying retinitis pigmentosa and myelodysplastic syndromes, and discuss how this knowledge may inform our understanding of craniofacial spliceosomopathies. Key Findings We describe the major diseases associated with mutations in proteins of the spliceosome. We review the current understanding of the mechanisms underlying two of these conditions, retinitis pigmentosa and myelodysplastic syndromes. We discuss how this information may direct further studies to dissect the etiology of spliceosomopathies affecting the craniofacial complex.
ISSN:1058-8388
1097-0177
DOI:10.1002/dvdy.214