title: The pre-mRNA-splicing factor SF3a66 functions as a microtubule-binding and -bundling protein.
abstract: SF3a (splicing factor 3a) complex is an essential component of U2 snRNPs (small nuclear ribonucleoprotein particles), which are involved in pre-mRNA splicing. This complex consists of three subunits: SF3a60, SF3a66 and SF3a120. Here, we report a possible non-canonical function of a well-characterized RNA-splicing factor, SF3a66. Ectopic expression experiments using each SF3a subunit in N1E 115 neuroblastoma cells reveals that SF3a66 alone can induce neurite extension, suggesting that SF3a66 functions in the regulation of cell morphology. A screen for proteins that bind to SF3a66 clarifies that SF3a66 binds to beta-tubulin, and also to microtubules, with high affinity, indicating that SF3a66 is a novel MAP (microtubule-associated protein). Electron microscopy experiments show that SF3a66 can bundle microtubules, and that bundling of microtubules is due to cross-bridging of microtubules by high-molecular-mass complexes of oligomerized SF3a66. These results indicate that SF3a66 is likely to be a novel MAP, and can function as a microtubule-bundling protein independently of RNA splicing.
authors.affiliation: Division of Cancer Genomics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takenaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miki
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D009447:Neuroblastoma / Q000737:chemistry / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D021122:Protein Subunits / Q000502:physiology; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000502:physiology; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000502:physiology*; D017411:Ribonucleoproteins, Small Nuclear; D014404:Tubulin / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D021122:Protein Subunits; D012322:RNA Precursors; D017413:Ribonucleoprotein, U2 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D014404:Tubulin; C088049:splicing factor 3a