title: Time-resolved quantitative proteomics implicates the core snRNP protein SmB together with SMN in neural trafficking.
abstract: The biogenesis of splicing snRNPs (small nuclear ribonucleoproteins) is a complex process, beginning and ending in the nucleus of the cell but including key stages that take place in the cytoplasm. In particular, the SMN (survival motor neuron) protein complex is required for addition of the core Sm proteins to the snRNP. Insufficiency of SMN results in the inherited neurodegenerative condition, spinal muscular atrophy (SMA). Details of the physical organization of the cytoplasmic stages of snRNP biogenesis are unknown. Here, we use time-resolved quantitative proteomics to identify proteins that associate preferentially with either newly assembled or mature splicing snRNPs. We identified highly mobile SmB protein-trafficking vesicles in neural cells, which are dependent on the cellular levels of SMN and SmB for their morphology and mobility. We propose that these represent a family of related vesicles, some of which play a role in snRNP biogenesis and some that might play more diverse roles in cellular RNA metabolism.
authors.affiliation: College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Prescott
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bales
authors.forename: John
authors.initials: J
authors.lastname: James
authors.forename: Laura
authors.initials: L
authors.lastname: Trinkle-Mulcahy
authors.forename: Judith E
authors.initials: JE
authors.lastname: Sleeman
mesh_terms: D004398:Dyneins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D012326:RNA Splicing; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism*; D059008:Time-Lapse Imaging; D022161:Transport Vesicles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism; D055517:snRNP Core Proteins / Q000378:metabolism*
chemical_list: D020543:Proteome; C526471:SMN1 protein, human; C526407:SNRPB protein, human; D055533:Survival of Motor Neuron 1 Protein; D033921:Vesicular Transport Proteins; D055517:snRNP Core Proteins; D004398:Dyneins
keywords: SILAC protemics; SMN; Spinal muscular atrophy; Survival of motor neuron protein; Vesicles; snRNPs