Alternative titles; symbols
HGNC Approved Gene Symbol: COIL
Cytogenetic location: 17q22 Genomic coordinates (GRCh38): 17:56,938,199-56,961,050 (from NCBI)
The nuclear coiled body (CB) was initially described as an accessory body to the nucleolus in light microscopy by the Spanish cytologist Ramon y Cajal using the silver staining method. In the late 1960s, the CB was characterized by electron microscopy as a morphologic structure distinct from other nuclear bodies. CBs are noncapsular structures with a diameter of 0.3 to 1.0 micron and are loosely packed with threads that have the appearance of coils. Human autoimmune antibodies to CBs recognize an 80-kD nuclear protein called p80-coilin. Affinity-purified antibodies to the 80-kD protein show highly specific immunostaining, suggesting that p80-coilin is an integral component of the coiled body. CBs are known to assemble and disassemble during the cell cycle, with the highest number of CBs occurring at mid to late G1. In S and G2 phases, CBs become larger and their number decreases; they are often undetectable during mitosis. Using a human autoantibody as a probe for expression cloning, Chan et al. (1994) isolated a partial cDNA encoding p80-coilin. The 5-prime end of the complete cDNA was obtained using 5-prime RACE. A 2.7-kb mRNA was detected in Northern blot analysis. The complete p80-coilin protein contains 576 amino acids and has a predicted molecular mass of 62,608 Da. A putative pseudogene was also detected.
CBs and nuclear structures known as gems contain high concentrations of the survival motor neurons (SMN) protein complex (see SMN1; 600354). CBs and gems often colocalize, and communication between them is mediated by coilin, the CB marker. Hebert et al. (2002) identified symmetric dimethylarginine residues within the coilin RG box motif and found that mutation of arginines within the coilin RG box resulted in gem formation. Coilin was undermethylated in HeLa cells that often displayed gems, but not in HeLa cells that primarily contained CBs. Similarly, extracts prepared from cells that displayed gems were less efficient in methylating Sm (see SNRPN2; 601061) and coilin RG box motifs in vitro. Inhibition of protein methylation in vivo and in vitro decreased the affinity of the coilin interaction with SMN. Hebert et al. (2002) concluded that symmetrical dimethylation of the coilin RG box motif is a molecular switch that determines whether the SMN complex forms gems or becomes incorporated into CBs.
By yeast 2-hybrid analysis, Hong et al. (2003) found that ataxin-1 (ATXN1; 601556) interacted with coilin. Mutation analysis indicated that the C-terminal regions of both proteins mediated the interaction. HeLa cells cotransfected with ataxin-1 and coilin showed colocalization of the 2 proteins in aggregates in the nucleoplasm. A mutant form of ataxin-1 containing a polyglutamine expansion associated with spinocerebellar ataxia-1 (SCA1; 164400) also interacted with coilin and localized with some coiled bodies, but it had no effect on their normal nuclear distribution.
Using yeast 2-hybrid screens, coaffinity purification analysis of transfected HEK293 cells, and bioinformatic analysis, Lim et al. (2006) developed an interaction network for 54 human proteins involved in 23 inherited ataxias. By database analysis, they expanded the core network to include more distantly related interacting proteins that could function as genetic modifiers. Within this network, COIL interacted with ATXN1 and with the ataxia-associated protein puratrophin-1 (PLEKHG4; 609526).
Kaiser et al. (2008) showed that the Cajal body can be formed de novo. Immobilization on chromatin of both Cajal body structural components, such as coilin, and functional components of the Cajal body, such as the SMN complex, spliceosomal small nuclear ribonucleoproteins (RNPs), small nucleolar RNPs, and small Cajal body-specific RNPs, is sufficient for the formation of a morphologically normal and apparently functional Cajal body. Kaiser et al. (2008) concluded that biogenesis of the Cajal body does not follow a hierarchical assembly pathway and exhibits hallmarks of a self-organizing structure.
Chan et al. (1994) determined that the COIL gene contains 7 exons and spans approximately 25 kb.
By fluorescence in situ hybridization, Chan et al. (1994) localized the COIL gene to 17q22-q23.
Tucker et al. (2001) created knockout mice lacking the C-terminal 487 amino acids of coilin. Mutant mice showed reduced viability, but otherwise appeared normal. Tissues and cell lines derived from mutant embryos retained extranucleolar foci that were similar in size and shape to CBs and contained fibrillarin (FBL; 134795) and Nopp140 (602394), but not other typical nucleolar markers. However, these 'residual' CBs failed to concentrate Sm proteins required for splicing small nuclear ribonucleoproteins (snRNPs), and they failed to attract members of the SMN complex. Transient expression of wildtype mouse coilin in knockout cells resulted in the formation of structures that appeared to be fully intact CBs, capable of recruiting both Sm snRNPs and the SMN complex, as well as a more diffuse accumulation of coilin protein that appeared to lack all other CB components. Tucker et al. (2001) concluded that coilin is required for recruitment of SMN complex proteins and splicing snRNPs to CBs.
Chan, E. K. L., Takano, S., Andrade, L. E. C., Hamel, J. C., Matera, A. G. Structure, expression and chromosomal localization of human p80-coilin gene. Nucleic Acids Res. 22: 4462-4469, 1994. [PubMed: 7971277] [Full Text: https://doi.org/10.1093/nar/22.21.4462]
Hebert, M. D., Shpargel, K. B., Ospina, J. K., Tucker, K. E., Matera, A. G. Coilin methylation regulates nuclear body formation. Dev. Cell 3: 329-337, 2002. [PubMed: 12361597] [Full Text: https://doi.org/10.1016/s1534-5807(02)00222-8]
Hong, S., Ka, S., Kim, S., Park, Y., Kang, S. p80 coilin, a coiled body-specific protein, interacts with ataxin-1, the SCA1 gene product. Biochim. Biophys. Acta 1638: 35-42, 2003. [PubMed: 12757932] [Full Text: https://doi.org/10.1016/s0925-4439(03)00038-3]
Kaiser, T. E., Intine, R. V., Dundr, M. De novo formation of a subnuclear body. Science 322: 1713-1717, 2008. [PubMed: 18948503] [Full Text: https://doi.org/10.1126/science.1165216]
Lim, J., Hao, T., Shaw, C., Patel, A. J., Szabo, G., Rual, J.-F., Fisk, C. J., Li, N., Smolyar, A., Hill, D. E., Barabasi, A.-L., Vidal, M., Zoghbi, H. Y. A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 125: 801-814, 2006. [PubMed: 16713569] [Full Text: https://doi.org/10.1016/j.cell.2006.03.032]
Tucker, K. E., Berciano, M. T., Jacobs, E. Y., LePage, D. F., Shpargel, K. B., Rossire, J. J., Chan, E. K. L., Lafarga, M., Conlon, R. A., Matera, A. G. Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product. J. Cell Biol. 154: 293-307, 2001. [PubMed: 11470819] [Full Text: https://doi.org/10.1083/jcb.200104083]