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Nat Ecol Evol. 2019 Apr;3(4):691-701. doi: 10.1038/s41559-019-0813-6. Epub 2019 Mar 4.

A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons.

Author information

1
Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.
2
Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
3
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
4
Sars Centre for Marine Molecular Biology, University of Bergen, Bergen, Norway.
5
Centro Andaluz de Biología del Desarrollo, CSIC-Universidad Pablo de Olavide-Junta de Andalucía, Seville, Spain.
6
School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK.
7
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
8
Universitat Pompeu Fabra, Barcelona, Spain.
9
Department of Biological Sciences, University of Bergen, Bergen, Norway.
10
ICREA, Barcelona, Spain.
11
Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain. mirimia@gmail.com.
12
Universitat Pompeu Fabra, Barcelona, Spain. mirimia@gmail.com.
13
ICREA, Barcelona, Spain. mirimia@gmail.com.

Abstract

The mechanisms by which entire programmes of gene regulation emerged during evolution are poorly understood. Neuronal microexons represent the most conserved class of alternative splicing in vertebrates, and are critical for proper brain development and function. Here, we discover neural microexon programmes in non-vertebrate species and trace their origin to bilaterian ancestors through the emergence of a previously uncharacterized 'enhancer of microexons' (eMIC) protein domain. The eMIC domain originated as an alternative, neural-enriched splice isoform of the pan-eukaryotic Srrm2/SRm300 splicing factor gene, and subsequently became fixed in the vertebrate and neuronal-specific splicing regulator Srrm4/nSR100 and its paralogue Srrm3. Remarkably, the eMIC domain is necessary and sufficient for microexon splicing, and functions by interacting with the earliest components required for exon recognition. The emergence of a novel domain with restricted expression in the nervous system thus resulted in the evolution of splicing programmes that qualitatively expanded the neuronal molecular complexity in bilaterians.

Comment in

PMID:
30833759
DOI:
10.1038/s41559-019-0813-6
[Indexed for MEDLINE]

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