title: The relationship between SMN, the spinal muscular atrophy protein, and nuclear coiled bodies in differentiated tissues and cultured cells.
abstract: The spinal muscular atrophy protein, SMN, is a cytoplasmic protein that is also found in distinct nuclear structures called "gems." Gems are closely associated with nuclear coiled bodies and both may have a direct role in snRNP maturation and pre-RNA splicing. There has been some controversy over whether gems and coiled bodies colocalize or form adjacent/independent structures in HeLa and other cultured cells. Using a new panel of antibodies against SMN and antibodies against coilin-p80, a systematic and quantitative study of adult differentiated tissues has shown that gems always colocalize with coiled bodies. In some tissues, a small proportion of coiled bodies (<10%) had no SMN, but independent or adjacent gems were not found. The most striking observation, however, was that many cell types appear to have neither gems nor coiled bodies (e.g., cardiac and smooth muscle, blood vessels, stomach, and spleen) and this expression pattern is conserved across human, rabbit, and pig species. This shows that assembly of distinct nuclear bodies is not essential for RNA splicing and supports the view that they may be storage sites for reserves of essential proteins and snRNPs. Overexpression of SMN in COS-7 cells produced supernumerary nuclear bodies, most of which also contained coilin-p80, confirming the close relationship between gems and coiled bodies. However, when SMN is reduced to very low levels in type I SMA fibroblasts, coiled bodies are still formed. Overall, the data suggest that gem/coiled body formation is not determined by high cytoplasmic SMN concentrations or high metabolic activity alone and that a differentiation-specific factor may control their formation.
authors.affiliation: MRIC Biochemistry Group, North East Wales Institute, Mold Road, Wrexham, LL11 2AW, United Kingdom.
authors.forename: P J
authors.initials: PJ
authors.lastname: Young
authors.forename: T T
authors.initials: TT
authors.lastname: Le
authors.forename: N
authors.initials: N
authors.lastname: thi Man
authors.forename: A H
authors.initials: AH
authors.lastname: Burghes
authors.forename: G E
authors.initials: GE
authors.lastname: Morris
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D020541:Coiled Bodies / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D017362:Cyclic AMP Response Element-Binding Protein; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009134:Muscular Atrophy, Spinal; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D016601:RNA-Binding Proteins; D011817:Rabbits; D055532:SMN Complex Proteins; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D013552:Swine
chemical_list: D000911:Antibodies, Monoclonal; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C068921:p80-coilin