snRNP proteins in health and disease
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
29037818
DOI
10.1016/j.semcdb.2017.10.011
PII: S1084-9521(17)30150-7
Knihovny.cz E-resources
- Keywords
- Congenital craniofacial disorders, Haematological malignancies, Mutations, Retinopathy, Spliceosome,
- MeSH
- Cryoelectron Microscopy MeSH
- Protein Conformation MeSH
- Humans MeSH
- Mutation MeSH
- Disease genetics MeSH
- RNA Precursors genetics MeSH
- Ribonucleoproteins, Small Nuclear chemistry genetics ultrastructure MeSH
- RNA Splicing * MeSH
- Spliceosomes genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- RNA Precursors MeSH
- Ribonucleoproteins, Small Nuclear MeSH
Split gene architecture of most human genes requires removal of intervening sequences by mRNA splicing that occurs on large multiprotein complexes called spliceosomes. Mutations compromising several spliceosomal components have been recorded in degenerative syndromes and haematological neoplasia, thereby highlighting the importance of accurate splicing execution in homeostasis of assorted adult tissues. Moreover, insufficient splicing underlies defective development of craniofacial skeleton and upper extremities. This review summarizes recent advances in the understanding of splicing factor function deduced from cryo-EM structures. We combine these data with the characterization of splicing factors implicated in hereditary or somatic disorders, with a focus on potential functional consequences the mutations may elicit in spliceosome assembly and/or performance. Given aberrant splicing or perturbations in splicing efficiency substantially underpin disease pathogenesis, profound understanding of the mis-splicing principles may open new therapeutic vistas. In three major sections dedicated to retinal dystrophies, hereditary acrofacial syndromes, and haematological malignancies, we delineate the noticeable variety of conditions associated with dysfunctional splicing and accentuate recurrent patterns in splicing defects.
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