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Gene Review

unc-22  -  Protein UNC-22

Caenorhabditis elegans

 
 
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Disease relevance of unc-22

  • A polyclonal antibody raised against an Escherichia coli beta-galactosidase-unc-22 fusion protein recognizes a polypeptide in nematode extracts that is between 500,000 and 600,000 daltons and labels the muscle A-band in indirect immunofluorescent microscopy [1].
 

High impact information on unc-22

  • Reversion analysis of mutants of unc-22 IV, a gene affecting muscle structure and function in Caenorhabditis elegans, led to the isolation of six extragenic dominant suppressors of the "twitching" phenotype of unc-22 mutants [2].
  • The location of the protein in the A-band, along with earlier genetic data, suggests that the unc-22 product may interact with myosin to regulate its function [1].
  • The unc-22 gene is one of a set of genes identified using classical genetics that affect muscle structure and function in the free-living nematode Caenorhabditis elegans [1].
  • To examine the mutagenic spectrum of 4,5',8-trimethylpsoralen (TMP) in Caenorhabditis elegans, we isolated mutations in the unc-22 and pal-1 genes following TMP mutagenesis and analyzed them for restriction fragment length polymorphisms by Southern blot [3].
  • Bergerac has as one of its targets unc-22, a previously uncloned gene on chromosome IV important in assembly and function of the body wall musculature [4].
 

Biological context of unc-22

  • We have examined several of the unc-22 antisense plasmid transformed lines to determine the mechanistic basis for the observed phenotypes [5].
  • Four genes are shown by multifactor crosses to map to a 2-3 map unit interval between unc-24 and unc-22 on chromosome IV [6].
  • The objective of this paper was the identification and characterization of coding regions in four cosmids containing DNA from the interval between dpy-20 and unc-22 on linkage group IV [7].
  • For example, the C. elegans ges-1 5'-flanking region (as well as several introns) contains copies of three different SINE-like sequences, previously identified near the hsp-16 genes, near the unc-22 gene and in a repetitive element CeRep-3; none of these elements are found in the C. briggsae ges-1 gene [8].
  • We believe that two of the essential genes identified in this study, let-56 and let-52, are the adjacent genes on either side of unc-22 [9].
 

Anatomical context of unc-22

 

Associations of unc-22 with chemical compounds

  • Because the BO strain is rich in Tc1 insertion sites and the N2 strain has few, the majority of Tc1-bearing genomic fragments in the constructed strain were derived from the unc-22 region [11].
  • Five formaldehyde-induced deficiencies that uncover unc-22 IV, a gene affecting muscle structure in the nematode Caenorhabditis elegans were isolated and positioned [9].
  • Thirty-seven ethyl methane-sulfonate-induced lethal and sterile mutations linked to unc-22 were isolated and tested for complementation with sDf2 [9].
  • TMP is not very potent, but a large proportion of TMP-induced unc-22 mutations are small deletions [12].
  • Several approaches were taken to measure mutational changes that occurred during the spaceflight including measurement of the integrity of poly-G/poly-C tracts, determination of the mutation frequency in the unc-22 gene, analysis of lethal mutations captured by the genetic balancer eT1(III;V), and identification of alterations in telomere length [13].
 

Other interactions of unc-22

  • The region around the twitcher gene, unc-22, flanked by unc-43 on the left and by unc-31 on the right, has been intensively studied in our laboratory over the period of the last 8 years [11].
  • These animals have phenotypes consistent with reduction and/or elimination of function of the gene to which antisense RNA has been produced: twitching and disorganization of muscle filaments for the unc-22 antisense constructs and lack of muscle tone, slow movement, and egg laying defects for the unc-54 antisense constructs [5].
  • Partial sequence analysis of unc-22 has previously revealed that its encoded polypeptide, named twitchin, consists of a single protein kinase domain and multiple copies of both an immunoglobulin-like domain and a fibronectin type III-like domain [14].
  • To demonstrate its utility we knocked down unc-22 in body wall muscles as well as the axon guidance gene unc-5 in the nervous system indicating that promoter-driven hairpins can overcome the neuronal resistance to RNAi [15].
 

Analytical, diagnostic and therapeutic context of unc-22

References

  1. Identification and intracellular localization of the unc-22 gene product of Caenorhabditis elegans. Moerman, D.G., Benian, G.M., Barstead, R.J., Schriefer, L.A., Waterston, R.H. Genes Dev. (1988) [Pubmed]
  2. Mutations in the unc-54 myosin heavy chain gene of Caenorhabditis elegans that alter contractility but not muscle structure. Moerman, D.G., Plurad, S., Waterston, R.H., Baillie, D.L. Cell (1982) [Pubmed]
  3. Trimethylpsoralen induces small deletion mutations in Caenorhabditis elegans. Yandell, M.D., Edgar, L.G., Wood, W.B. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  4. Molecular cloning of the muscle gene unc-22 in Caenorhabditis elegans by Tc1 transposon tagging. Moerman, D.G., Benian, G.M., Waterston, R.H. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  5. Production of antisense RNA leads to effective and specific inhibition of gene expression in C. elegans muscle. Fire, A., Albertson, D., Harrison, S.W., Moerman, D.G. Development (1991) [Pubmed]
  6. Genetic mapping of Caenorhabditis elegans collagen genes using DNA polymorphisms as phenotypic markers. Cox, G.N., Carr, S., Kramer, J.M., Hirsh, D. Genetics (1985) [Pubmed]
  7. Evolutionarily conserved coding sequences in the dpy-20-unc-22 region of Caenorhabditis elegans. Prasad, S.S., Baillie, D.L. Genomics (1989) [Pubmed]
  8. The gut esterase gene (ges-1) from the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. Kennedy, B.P., Aamodt, E.J., Allen, F.L., Chung, M.A., Heschl, M.F., McGhee, J.D. J. Mol. Biol. (1993) [Pubmed]
  9. Essential genes and deficiencies in the unc-22 IV region of Caenorhabditis elegans. Rogalski, T.M., Moerman, D.G., Baillie, D.L. Genetics (1982) [Pubmed]
  10. Genetic analysis and complementation by germ-line transformation of lethal mutations in the unc-22 IV region of Caenorhabditis elegans. Clark, D.V., Baillie, D.L. Mol. Gen. Genet. (1992) [Pubmed]
  11. Cloning within the unc-43 to unc-31 interval (linkage group IV) of the Caenorhabditis elegans genome using Tc1 linkage selection. Baillie, D.L., Beckenbach, K.A., Rose, A.M. Can. J. Genet. Cytol. (1985) [Pubmed]
  12. Mutagenesis. Anderson, P. Methods Cell Biol. (1995) [Pubmed]
  13. A mutational analysis of Caenorhabditis elegans in space. Zhao, Y., Lai, K., Cheung, I., Youds, J., Tarailo, M., Tarailo, S., Rose, A. Mutat. Res. (2006) [Pubmed]
  14. Additional sequence complexity in the muscle gene, unc-22, and its encoded protein, twitchin, of Caenorhabditis elegans. Benian, G.M., L'Hernault, S.W., Morris, M.E. Genetics (1993) [Pubmed]
  15. pWormgatePro enables promoter-driven knockdown by hairpin RNA interference of muscle and neuronal gene products in Caenorhabditis elegans. Briese, M., Esmaeili, B., Johnson, N.M., Sattelle, D.B. Invert. Neurosci. (2006) [Pubmed]
 
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