Identification and Comparison of Motifs in Brain-Specific and Muscle-Specific Alternative Splicing

ABSTRACT Precise and robust regulation of alternative splicing provides cells with an essential means of gene expression control. However, the mechanisms that ensure the tight control of tissue-specific alternative splicing are not well understood. It has been demonstrated that robust regulation often results from the contributions of multiple factors to one particular splicing pathway. We report here a novel strategy used by a single splicing regulator that blocks the formation of two distinct prespliceosome complexes to achieve efficient regulation. Fox-1/Fox-2 proteins, potent regulators of alternative splicing in the heart, skeletal muscle, and brain, repress calcitonin-specific splicing of the calcitonin/CGRP pre-mRNA. Using biochemical analysis, we found that Fox-1/Fox-2 proteins block prespliceosome complex formation at two distinct steps through binding to two functionally important UGCAUG elements. First, Fox-1/Fox-2 proteins bind to the intronic site to inhibit SF1-dependent E′ complex formation. Second, these proteins bind to the exonic site to block the transition of E′ complex that escaped the control of the intronic site to E complex. These studies provide evidence for the first example of regulated E′ complex formation. The two-step repression of presplicing complexes by a single regulator provides a powerful and accurate regulatory strategy.

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Tissue-specific alternative splicing of BK channel transcripts in Drosophila

Genes Brain & Behavior ◽

10.1111/j.1601-183x.2005.00164.x ◽

2006 ◽

Vol 5 (4) ◽

pp. 329-339 ◽

Cited By ~ 10

Author(s):

J. Y. Yu ◽

A. B. Upadhyaya ◽

N. S. Atkinson

Keyword(s):

Alternative Splicing ◽

Bk Channel ◽

Tissue Specific ◽

Specific Alternative

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Genome-wide detection of testis- and testicular cancer-specific alternative splicing

Carcinogenesis ◽

10.1093/carcin/bgm194 ◽

2007 ◽

Vol 28 (12) ◽

pp. 2484-2490 ◽

Cited By ~ 14

Author(s):

Chunjiang He ◽

Zhixiang Zuo ◽

Hengling Chen ◽

Liao Zhang ◽

Fang Zhou ◽

...

Keyword(s):

Alternative Splicing ◽

Testicular Cancer ◽

Genome Wide ◽

Specific Alternative

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DoChaP: The Domain Change Presenter

10.1101/2020.12.16.423045 ◽

2020 ◽

Author(s):

Shani T. Gal-Oz ◽

Nimrod Haiat ◽

Dana Eliyahu ◽

Guy Shani ◽

Tal Shay

Keyword(s):

Alternative Splicing ◽

Rna Splicing ◽

Protein Domains ◽

Visual Presentation ◽

Structural Effect ◽

Protein Isoforms ◽

Multiple Transcripts ◽

Genome Wide ◽

Health And Disease ◽

Specific Alternative

AbstractAlternative RNA splicing results in multiple transcripts of the same gene, possibly encoding for different protein isoforms with different protein domains and functionalities. Whereas it is possible to manually determine the effect of a specific alternative splicing event on the domain composition of a particular encoded protein, the process requires the tedious integration of several data sources; it is therefore error prone and its implementation is not feasible for genome-wide characterization of domains affected by differential splicing. To fulfill the need for an automated solution, we developed the Domain Change Presenter (DoChaP), a web server for the visualization of the exon–domain association. DoChaP visualizes all transcripts of a given gene, the domains of the proteins that they encode, and the exons encoding each domain. The visualization enables a comparison between the transcripts and between the protein isoforms they encode for. The organization and visual presentation of the information makes the structural effect of each alternative splicing event on the protein structure easily identified. To enable a study of the conservation of the exon structure, alternative splicing, and the effect of alternative splicing on protein domains, DoChaP also facilitates an inter-species comparison of domain–exon associations. DoChaP thus provides a unique and easy-to-use visualization of the exon–domain association and its conservation between transcripts and orthologous genes and will facilitate the study of the functional effects of alternative splicing in health and disease.

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