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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
Understanding the molecular pathways disrupted in motor neuron diseases is urgently needed. Here, we employed CRISPR knockout (KO) to investigate the functions of four ALS-causative RNA/DNA binding pr...
The spliceosome catalyses the excision of introns from pre-mRNA in two steps, branching and exon ligation, and is assembled from five small nuclear ribonucleoprotein particles (snRNPs; U1, U2, U4, U5,...
The pre-catalytic spliceosome (B complex) is preceded by its precursor spliceosome (pre-B complex) and followed by the activated spliceosome (B complex). The pre-B-to-B and B-to-B transitions are driv...
Elucidating the complete network of protein-protein interactions, or interactome, is a fundamental goal of the post-genomic era, yet existing interactome maps are far from complete. To increase the th...
Proteomics aids to the discovery and expansion of protein-protein interaction networks, which are key to understand molecular mechanisms in physiology and physiopathology, but also to infer protein fu...
This investigation is being carried out to learn more about research findings from a study that was completed last year. Those findings revealed that within the skeletal muscle cells of i...
For the purposes of this study, as a core lab coordinating center, the investigators will be performing P31 MRS core lab analyses; hormone core lab analyses; lipid core lab analyses; gluco...
Infants/children with cow's milk allergy will take part in 2 double-blinded placebo-controlled food challenges (DBPCFC) of 2 extensively hydrolyzed formulas in random order. If both food c...
The purpose of this study is to assess growth in infants who are fed an extensively hydrolyzed formula.
Previous work performed by University of New Mexico Comprehensive Cancer Center (UNMCCC) investigators has revealed previously unknown genomic mutations in children, adolescents, and young...
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.
HLA-DR antigen subtypes that have been classified according to their affinity to specific ANTIBODIES. The DNA sequence analyses of HLA-DR ALPHA-CHAINS and HLA-DR BETA-CHAINS has for the most part revealed the specific alleles that are responsible for each serological subtype.
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...