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

Research output: Contribution to journalArticlepeer-review

Authors

  • Antonio Torres-Mendez
  • Sophie Bonnal
  • Yamile Marquez
  • Jonathan Roth
  • Marta Iglesias
  • Jon Permanyer
  • Isabel Almundi
  • Dave O'Hanlon
  • Tanit Guitart
  • Anne-Claude Gingras
  • Fátima Gebauer
  • Fabian Rentzsch
  • Benjamin J. Blencowe
  • Juan Valcárcel
  • Manuel Irimia

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)691–701
Number of pages11
JournalNature Ecology and Evolution
Volume3
Early online date4 Mar 2019
Publication statusPublished - 2019

Keywords

  • complexity, genome evolution, transcriptomics, nervous system