Time-resolved quantitative proteomics implicates the core snRNP protein, SmB, together with the Survival of Motor Neuron protein, 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 timeresolved 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.

The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly

“…The contributions of each of these individual processes remain to be fully evaluated, however the dysregulation of all of these processes taken together likely explains the unique onset and presentation of the disease. For mRNP localization in particular, it remains to be seen how this manifests in vivo , and if local translation defects reported upon SMN deficiency (Fallini et al, 2016) stem from reductions in RNA delivery or from a direct role for SMN in axonal protein synthesis itself (Dombert et al, 2014; Kye et al, 2014; Prescott et al, 2014; Rage et al, 2013; Zhang et al, 2006). The observed defect in mRNP assembly in the cell body occurs upstream of the previously characterized localization defects, which then result in decreased local translation.…”

The Comparative Utility of Viromer RED and Lipofectamine for Transient Gene Introduction into Glial Cells

“…Further optimization of cell seeding densities or complexation parameters for different cell systems may provide a way to reduce these negative effects on cell viability [ 45 , 46 ]. Viromer technology has been further developed to suit the needs of different biomolecules (plasmid DNA, siRNA) and has been investigated previously on both neuronal (SHSY5Y) and nonneuronal cell lines (Ramos, RAW264.7 macrophages) [ 47 – 51 ].…”

c‐Myc‐mediated SNRPB upregulation functions as an oncogene in hepatocellular carcinoma

“…This suggests that SNRPB may play an essential role in cell division and DNA replication. Interestingly, a previous study showed that SNRPB interacted with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) (Prescott et al, 2014), a subunit of human cytoplasmic dynein complex that functions in intracellular transport of DNA damage proteins and mitotic spindle positioning in colorectal cancer (Sucularli and Arslantas, 2017). GESA data suggest SNRPB's participation in cell cycle regulation which is largely mediated by the tumor suppressor p53.…”