RNA splicing: group I intron crystal structures reveal the basis of splice site selection and metal ion catalysis

2006 ◽  
Vol 16 (3) ◽  
pp. 319-326 ◽  
Author(s):  
Mary R Stahley ◽  
Scott A Strobel
Keyword(s):  
Crystal Structures ◽  
Splice Site ◽  
Site Selection ◽  
Rna Splicing ◽  
Metal Ion ◽  
Group I Intron ◽  
Splice Site Selection ◽  
Group I ◽  
Metal Ion Catalysis

scholarly journals Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hisashi Yoshida ◽  
Sam-Yong Park ◽  
Gyosuke Sakashita ◽  
Yuko Nariai ◽  
Kanako Kuwasako ◽  
...  
Keyword(s):  
Splice Site ◽  
Site Selection ◽  
Rna Splicing ◽  
Single Amino Acid ◽  
Splice Site Selection ◽  
Aberrant Splicing ◽  
Serious Disease ◽  
New Treatments ◽  
Target Rna ◽  
Single Amino Acid Mutation

Abstract The accurate exclusion of introns by RNA splicing is critical for the production of mature mRNA. U2AF1 binds specifically to the 3´ splice site, which includes an essential AG dinucleotide. Even a single amino acid mutation of U2AF1 can cause serious disease such as certain cancers or myelodysplastic syndromes. Here, we describe the first crystal structures of wild-type and pathogenic mutant U2AF1 complexed with target RNA, revealing the mechanism of 3´ splice site selection, and how aberrant splicing results from clinically important mutations. Unexpected features of this mechanism may assist the future development of new treatments against diseases caused by splicing errors.

scholarly journals The anti-angiogenic isoforms of VEGF in health and disease

2009 ◽  
Vol 37 (6) ◽  
pp. 1207-1213 ◽  
Author(s):  
Yan Qiu ◽  
Coralie Hoareau-Aveilla ◽  
Sebastian Oltean ◽  
Steven J. Harper ◽  
David O. Bates
Keyword(s):  
Splice Site ◽  
Site Selection ◽  
Age Related Macular Degeneration ◽  
Splicing Factor ◽  
Splice Site Selection ◽  
Age Related ◽  
Normal Human ◽  
Radical Revision

Anti-angiogenic VEGF (vascular endothelial growth factor) isoforms, generated from differential splicing of exon 8, are widely expressed in normal human tissues but down-regulated in cancers and other pathologies associated with abnormal angiogenesis (cancer, diabetic retinopathy, retinal vein occlusion, the Denys–Drash syndrome and pre-eclampsia). Administration of recombinant VEGF165b inhibits ocular angiogenesis in mouse models of retinopathy and age-related macular degeneration, and colorectal carcinoma and metastatic melanoma. Splicing factors and their regulatory molecules alter splice site selection, such that cells can switch from the anti-angiogenic VEGFxxxb isoforms to the pro-angiogenic VEGFxxx isoforms, including SRp55 (serine/arginine protein 55), ASF/SF2 (alternative splicing factor/splicing factor 2) and SRPK (serine arginine domain protein kinase), and inhibitors of these molecules can inhibit angiogenesis in the eye, and splice site selection in cancer cells, opening up the possibility of using splicing factor inhibitors as novel anti-angiogenic therapeutics. Endogenous anti-angiogenic VEGFxxxb isoforms are cytoprotective for endothelial, epithelial and neuronal cells in vitro and in vivo, suggesting both an improved safety profile and an explanation for unpredicted anti-VEGF side effects. In summary, C-terminal distal splicing is a key component of VEGF biology, overlooked by the vast majority of publications in the field, and these findings require a radical revision of our understanding of VEGF biology in normal human physiology.

Are vertebrate exons scanned during splice-site selection?

Nature ◽  
1992 ◽  
Vol 360 (6401) ◽  
pp. 277-280 ◽  
Author(s):  
Maho Niwa ◽  
Clinton C. MacDonald ◽  
Susan M. Berget
Keyword(s):  
Splice Site ◽  
Site Selection ◽  
Splice Site Selection
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