Interactome analyses revealed that the U1 snRNP machinery overlaps extensively with the RNAP II machinery and contains multiple ALS/SMA-causative proteins

Sci Rep. 2018 Jun 8;8(1):8755. doi: 10.1038/s41598-018-27136-3.


Mutations in multiple RNA/DNA binding proteins cause Amyotrophic Lateral Sclerosis (ALS). Included among these are the three members of the FET family (FUS, EWSR1 and TAF15) and the structurally similar MATR3. Here, we characterized the interactomes of these four proteins, revealing that they largely have unique interactors, but share in common an association with U1 snRNP. The latter observation led us to analyze the interactome of the U1 snRNP machinery. Surprisingly, this analysis revealed the interactome contains ~220 components, and of these, >200 are shared with the RNA polymerase II (RNAP II) machinery. Among the shared components are multiple ALS and Spinal muscular Atrophy (SMA)-causative proteins and numerous discrete complexes, including the SMN complex, transcription factor complexes, and RNA processing complexes. Together, our data indicate that the RNAP II/U1 snRNP machinery functions in a wide variety of molecular pathways, and these pathways are candidates for playing roles in ALS/SMA pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism
  • HeLa Cells
  • Humans
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Protein Interaction Maps*
  • RNA Polymerase II / metabolism*
  • RNA-Binding Protein EWS / metabolism*
  • RNA-Binding Protein FUS / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Ribonucleoprotein, U1 Small Nuclear / metabolism*
  • TATA-Binding Protein Associated Factors / metabolism*


  • EWSR1 protein, human
  • FUS protein, human
  • MATR3 protein, human
  • Nuclear Matrix-Associated Proteins
  • RNA-Binding Protein EWS
  • RNA-Binding Protein FUS
  • RNA-Binding Proteins
  • Ribonucleoprotein, U1 Small Nuclear
  • TAF15 protein, human
  • TATA-Binding Protein Associated Factors
  • RNA Polymerase II