Protein modularity of alternatively spliced exons is associated with tissue-specific regulation of alternative splicing

Yi Xing ¹, Christopher J Lee

⁰Molecular Biology Institute, Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA.

Plos Genetics +

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September 20, 2005

View abstract on PubMed

Summary

Modular exons, which are multiples of 3 nucleotides, are key to tissue-specific alternative splicing. These "tissue-switched" exons show significant conservation between humans and mice.

Area Of Science

Genomics
Molecular Biology
Bioinformatics

Background

Alternative splicing generates protein diversity.
Protein modularity, defined by exon length (multiples of 3 nucleotides), is linked to functional alternative splicing.
The role of modular exons in tissue-specific regulation remains unclear.

Purpose Of The Study

To investigate the association between protein modularity and tissue-specific alternative splicing.
To analyze microarray data for alternatively spliced exons across mouse tissues.
To determine if modularity is specific to tissue-switched alternative splicing events.

Main Methods

Analysis of microarray data for 3,126 alternatively spliced exons across ten mouse tissues.
Comparison of exon length (multiples of 3 nt) with alternative splicing patterns.
Assessment of exon conservation between human and mouse.

Main Results

Modular exons are strongly associated with tissue-specific alternative splicing.
Exons with dramatic changes in inclusion levels across tissues ("tissue-switched" exons) are highly modular and conserved.
Increased protein modularity is specifically linked to tissue-switched alternative splicing, not overall inclusion levels.

Conclusions

Protein modularity is a significant feature of tissue-specific alternative splicing.
"Tissue-switched" exons represent a functionally important class of modular exons.
These findings highlight the evolutionary significance of modular exons in tissue-specific gene regulation.

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