Spliceosomal component PRP-40 is a central regulator of microexon splicing

Cell Rep. 2021 Aug 3;36(5):109464. doi: 10.1016/j.celrep.2021.109464.


Microexons (≤27 nt) play critical roles in nervous system development and function but create unique challenges for the splicing machinery. The mechanisms of microexon regulation are therefore of great interest. We performed a genetic screen for alternative splicing regulators in the C. elegans nervous system and identify PRP-40, a core component of the U1 snRNP. RNA-seq reveals that PRP-40 is required for inclusion of alternatively spliced, but not constitutively spliced, exons. PRP-40 is particularly required for inclusion of neuronal microexons, and our data indicate that PRP-40 is a central regulator of microexon splicing. Microexons can be relieved from PRP-40 dependence by artificially increasing exon size or reducing flanking intron size, indicating that PRP-40 is specifically required for microexons surrounded by conventionally sized introns. Knockdown of the orthologous PRPF40A in mouse neuroblastoma cells causes widespread dysregulation of microexons but not conventionally sized exons. PRP-40 regulation of neuronal microexons is therefore a widely conserved phenomenon.

Keywords: Microexon; PRP-40; PRPF40A; Spliceosome; Splicing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing* / genetics
  • Animals
  • Base Sequence
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / genetics
  • Epistasis, Genetic
  • Exons* / genetics
  • Nerve Net / metabolism
  • Protein Binding
  • RNA-Binding Proteins / metabolism
  • Spliceosomes* / metabolism
  • Transcriptome / genetics


  • Caenorhabditis elegans Proteins
  • RNA-Binding Proteins
  • PRP-40 protein, C elegans