title: Nuclear gems and Cajal (coiled) bodies in fetal tissues: nucleolar distribution of the spinal muscular atrophy protein, SMN.
abstract: SMN, the affected protein in spinal muscular atrophy (SMA), is a cytoplasmic protein that also occurs in nuclear structures called "gems" and is involved in snRNP maturation. Coilin-p80 is a marker protein for nuclear Cajal bodies (coiled bodies; CBs) which are also involved in snRNP maturation, storage or transport. We now show that gems and CBs are present in all fetal tissues, even those that lack gems/CBs in the adult. Most gems and CBs occur as separate nuclear structures in fetal tissues, but their colocalization increases with fetal age and is almost complete in the adult. In adult tissues, up to half of all gems/CBs are inside the nucleolus, whereas in cultured cells they are almost exclusively nucleoplasmic. The nucleolar SMN is often more diffusely distributed, compared with nucleoplasmic gems. Up to 30% of cells in fetal tissues have SMN distributed throughout the nucleolus, instead of forming gems in the nucleoplasm. The results suggest a function for gems distinct from Cajal bodies in fetal nuclei and a nucleolar function for SMN. Spinal cord, the affected tissue in SMA, behaves differently in several respects. In both fetal and adult motor neurons, many gems/CBs occur as larger bodies closely associated with the nucleolar perimeter. Uniquely in motor neurons, gems/CBs are more numerous in adult than in fetal stages and colocalization of gems and CBs occurs earlier in development. These unusual features of motor neurons may relate to their special sensitivity to reduced SMN levels in SMA patients.
authors: MRIC Biochemistry Group, North East Wales Institute, Mold Road, Wrexham LL11 2AW, United Kingdom.
authors: P J
authors: PJ
authors: Young
authors: T T
authors: TT
authors: Le
authors: M
authors: M
authors: Dunckley
authors: T M
authors: TM
authors: Nguyen
authors: A H
authors: AH
authors: Burghes
authors: G E
authors: GE
authors: Morris
mesh_terms: D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D002466:Cell Nucleolus / Q000737:chemistry*; D002467:Cell Nucleus / Q000737:chemistry*; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis; D020541:Coiled Bodies / Q000737:chemistry*; D017362:Cyclic AMP Response Element-Binding Protein; D003598:Cytoskeletal Proteins; D005333:Fetus / Q000737:chemistry* / Q000166:cytology; D006801:Humans; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D011817:Rabbits; D055532:SMN Complex Proteins; D017923:Sodium-Hydrogen Exchangers; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology; D014897:Spinal Muscular Atrophies of Childhood / Q000378:metabolism* / Q000473:pathology; D013552:Swine
chemical_list: D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D017362:Cyclic AMP Response Element-Binding Protein; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017923:Sodium-Hydrogen Exchangers; C047458:fibrillarin; C093376:sodium-hydrogen exchanger regulatory factor; C068921:p80-coilin