Changing transcriptional initiation sites and alternative 5′- and 3′-splice site selection of the first intron deploys Arabidopsis PROTEIN ISOASPARTYL METHYLTRANSFERASE2 variants to different subcellular compartments

2008 ◽  
Vol 55 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Randy D. Dinkins ◽  
Susmita Maitra Majee ◽  
Nihar R. Nayak ◽  
David Martin ◽  
Qilong Xu ◽  
...  
2004 ◽  
Vol 279 (16) ◽  
pp. 15799-15804 ◽  
Author(s):  
Autumn Massiello ◽  
Arelis Salas ◽  
Ryan L. Pinkerman ◽  
Patrick Roddy ◽  
James R. Roesser ◽  
...  

PLoS Genetics ◽  
2009 ◽  
Vol 5 (11) ◽  
pp. e1000717 ◽  
Author(s):  
Nurit Gal-Mark ◽  
Schraga Schwartz ◽  
Oren Ram ◽  
Eduardo Eyras ◽  
Gil Ast

2019 ◽  
Vol 47 (19) ◽  
pp. 10327-10339
Author(s):  
Nan-Ying Wu ◽  
Soo-Chen Cheng

Abstract The essential splicing factor Cwc24 contains a zinc-finger (ZF) domain required for its function in splicing. Cwc24 binds over the 5′ splice site after the spliceosome is activated, and its binding prior to Prp2-mediated spliceosome remodeling is important for proper interactions of U5 and U6 with the 5′ splice site sequence and selection of the 5′ splice site. Here, we show that Cwc24 transiently interacts with the 5′ splice site in formation of the functional RNA catalytic core during spliceosome remodeling, and the ZF-motif is required for specific interaction of Cwc24 with the 5′ splice site. Deletion of the ZF domain or mutation of the conserved ZF residues greatly weakened the association of Cwc24 with the spliceosome, and lowered the affinity and specificity of its interaction with the 5′ splice site, resulting in atypical interactions of U5, U6 and Prp8 with the 5′ splice site, and aberrant cleavage at the 5′ splice site. Our results reveal a crucial role of the Cwc24 ZF-motif for defining 5′ splice site selection in the first splicing step.


2006 ◽  
Vol 20 (10) ◽  
pp. 1680-1682 ◽  
Author(s):  
Autumn Massiello ◽  
James R. Roesser ◽  
Charles E. Chalfant ◽  
Autumn Massiello ◽  
James R. Roesser ◽  
...  

2009 ◽  
Vol 37 (6) ◽  
pp. 1207-1213 ◽  
Author(s):  
Yan Qiu ◽  
Coralie Hoareau-Aveilla ◽  
Sebastian Oltean ◽  
Steven J. Harper ◽  
David O. Bates

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.


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

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