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Published on: October 9, 2014
Evolution of Nova-dependent splicing regulation in the brain
Nejc Jelen1, Jernej Ule, Marko Zivin
1Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.
Plos Genetics
|October 17, 2007
Summary
The evolution of tissue-specific alternative splicing, particularly in the brain, is driven by changes in regulatory elements called YCAY clusters. Their presence predicts conserved splicing patterns across species, suggesting rapid evolution of these elements.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Genomics
Background:
- Alternative splicing generates diverse RNA molecules, with many exons exhibiting tissue-specific expression patterns.
- The evolutionary mechanisms underlying tissue-specific alternative splicing remain largely unexplored.
Purpose of the Study:
- To investigate the evolutionary conservation of neuron-specific splicing factors Nova1 and Nova2 and their regulated alternative exons.
- To understand the role of cis-acting elements (YCAY clusters) in the evolution of brain-specific splicing.
Main Methods:
- Comparative analysis of Nova1/Nova2 protein sequences and YCAY cluster conservation across vertebrate species (mouse, zebrafish, chicken).
- Examination of brain-specific alternative splicing patterns of Nova-regulated exons in zebrafish, chicken, and mouse.
Main Results:
- Nova RNA-binding domains show high conservation (94%) across vertebrates.
- Nova-dependent YCAY clusters exhibit significant divergence, with less than 50% conserved between mouse and zebrafish.
- Presence of YCAY clusters predicted conserved brain-specific splicing in lower vertebrates, while absence correlated with splicing loss.
Conclusions:
- Evolution of Nova-regulated splicing in higher vertebrates primarily involves changes in cis-acting elements (YCAY clusters).
- Tissue-specific splicing can evolve rapidly, potentially in a single step through YCAY cluster evolution.
- The conservation level of YCAY clusters is linked to the functional importance of the regulated RNAs.
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