Journal
CURRENT OPINION IN GENETICS & DEVELOPMENT
Volume 48, Issue -, Pages 57-66Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.gde.2017.10.008
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Funding
- National Institutes of Health [GM070503, GM117005]
- Edward P. Evans Foundation
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Pre-mRNA splicing factors recognize consensus signals within preliminary transcripts, and as cogs of the spliceosome machine, orchestrate the excision and rejoining of pre-mRNA regions for gene expression. Large-scale sequencing has demonstrated that mutations in key genes encoding pre-mRNA splicing factors are common among myeloid neoplasms and also occur in a variety of other cancers. This revelation offers new therapeutic opportunities to target pre-mRNA splicing vulnerabilities in hematologic and other malignancies. The mutated residues typically alter 30 splice site choice for a subset of transcripts. In this review, we highlight mechanistic insights from recent 3D structures that reveal the affected residues poised for pre-mRNA recognition.
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