TY - JOUR
T1 - A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons
AU - Torres-Mendez, Antonio
AU - Bonnal, Sophie
AU - Marquez, Yamile
AU - Roth, Jonathan
AU - Iglesias, Marta
AU - Permanyer, Jon
AU - Almundi, Isabel
AU - O'Hanlon, Dave
AU - Guitart, Tanit
AU - Soller, Matthias
AU - Gingras, Anne-Claude
AU - Gebauer, Fátima
AU - Rentzsch, Fabian
AU - Blencowe, Benjamin J.
AU - Valcárcel, Juan
AU - Irimia, Manuel
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - complexity
KW - genome evolution
KW - transcriptomics
KW - nervous system
UR - http://www.scopus.com/inward/record.url?scp=85062469652&partnerID=8YFLogxK
U2 - 10.1038/s41559-019-0813-6
DO - 10.1038/s41559-019-0813-6
M3 - Article
VL - 3
SP - 691
EP - 701
JO - Nature Ecology and Evolution
JF - Nature Ecology and Evolution
ER -