title: FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2.
abstract: Mutations in the RNA-binding protein FUS (fused in sarcoma)/TLS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the normal role of FUS is incompletely understood. We found that FUS binds the C-terminal domain (CTD) of RNA polymerase II (RNAP2) and prevents inappropriate hyperphosphorylation of Ser2 in the RNAP2 CTD at thousands of human genes. The loss of FUS leads to RNAP2 accumulation at the transcription start site and a shift in mRNA isoform expression toward early polyadenylation sites. Thus, in addition to its role in alternative RNA splicing, FUS has a general function in orchestrating CTD phosphorylation during RNAP2 transcription.
authors.affiliation: Howard Hughes Medical Institute.
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Schwartz
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Ebmeier
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Podell
authors.forename: Joseph
authors.initials: J
authors.lastname: Heimiller
authors.forename: Dylan J
authors.initials: DJ
authors.lastname: Taatjes
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cech
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D007074:Immunoglobulin G; D034702:RNA-Binding Protein FUS; D012694:Serine; D012319:RNA Polymerase II