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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.
This article was published in the following journal.
Name: Scientific reports
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A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U4-U6 snRNP along with the U5 snRNP preassemble into a single 25S particle that binds to the U1 and U2 snRNPs and the substrate to form mature SPLICEOSOMES. There is also evidence for the existence of individual U4 or U6 snRNPs in addition to their organization as a U4-U6 snRNP.
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A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U5 snRNP along with U4-U6 snRNP preassemble into a single 25S particle that binds to the U1 and U2 snRNPs and the substrate to form SPLICEOSOMES.
The study of disease in prehistoric times as revealed in bones, mummies, and archaeologic artifacts.
Critical analyses of books or other monographic works.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Polymerase Chain Reaction (PCR)
PCR (Polymerase Chain Reaction) uses the ability of DNA polymerase (enzymes that create DNA molecules by assembling nucleotides, the building blocks of DNA. These enzymes are essential to DNA replication and usually work in pairs to create two ident...