Disease relevance of unc-54

• Unlike deletions that occur in Escherichia coli, spontaneous unc-54 deletions did not contain statistically significant direct or inverted repeats at or near their termini [1].

High impact information on unc-54

• Placement of the three suppressor mutations s74, s77 and s95 on the genetic fine structure map of unc-54 demonstrates that they are clustered near the right end of the map [2].
• The amino acid sequence of the rod portion of nematode myosin, deduced for the sequence of the unc-54 heavy chain gene of Caenorhabditis elegans, is highly repetitive and has the characteristics of an alpha-helical coiled coil [3].
• Nonsense alleles of unc-54 express mRNAs that are unstable in smg(+) genetic backgrounds but have normal or near normal stability in smg(-) backgrounds. smg mutations also stabilize mRNA of unc-54(r293), a small deletion that removes the unc-54 polyadenylation site and expresses an aberrant mRNA [4].
• Because of disrupted MHC A assembly, dominant unc-54 mutants also exhibit a recessive-lethal phenotype [5].
• We have investigated Caenorhabditis elegans mutants in which altered unc-54 myosin heavy-chain protein interferes with assembly of thick myofilaments [5].

Biological context of unc-54

• Dominant unc-54 mutations occur at remarkably high frequency following ethylmethane sulfonate (EMS) mutagenesis; their frequency is approximately equal to that of recessive, loss-of-function mutations [5].
• The 1,966-amino acid unc-54 myosin heavy chain sequence was determined from DNA sequence studies of the cloned gene [6].
• Protein structural domains in the Caenorhabditis elegans unc-54 myosin heavy chain gene are not separated by introns [6].
• This unusually high gain-of-function frequency implies that many different amino acid substitutions in the myosin heavy-chain B protein can disrupt thick filament assembly [5].
• We have defined mutationally a number of essential genes near unc-54, and we have described the genetic fine structure of this region of linkage group I. As much as 27% of the unc-54 mutations induced by the bifunctional alkylating agent 1,2,7,8-diepoxyoctane are multisite deletions [7].

Anatomical context of unc-54

• The mutant MHC B also interferes with assembly of wild-type myosin heavy-chain A (MHC A), the product of another MHC gene expressed in body-wall muscle cells [5].
• In the wild type, a constant ratio of the synthesis of the unc-54-coded myosin B to myosin A, about 2:1, is maintained during the larval stages in which the synthesis of both myosins increases exponentially and rapid sarcomere growth and addition ensues [8].
• The genetic properties of Tc1 excision, combined with the DNA sequences of the resulting unc-54 alleles, demonstrated that excision was dependent on Tc1 transposition functions in both germ line and somatic cells [9].
• The deduced myosin II globular head amino acid sequence shows a high degree of similarity with the globular head sequences of the rat embryonic skeletal muscle and nematode unc 54 muscle myosins [10].

Associations of unc-54 with chemical compounds

• Two-thirds of the Tc1-containing introns removed from hlh-1 and unc-54 lack either the 5'-GU or AG-3' dinucleotides typically found at the termini of eukaryotic introns [11].

Regulatory relationships of unc-54

• In mutants that do not express MHC B or that express defective paramyosin, muscle structure is disrupted and movement is impaired [12].

Other interactions of unc-54

• Comparison of the unc-54 protein sequence with the sequence of a second myosin heavy chain from nematode, indicates that the globular head sequence S-1 is more highly conserved than the alpha-helical coiled-coil rod [6].
• 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 [13].
• The effects of mutation in the unc-52 locus are trans acting upon the synthesis of unc-54-coded myosin in a specific set of muscle cells during a defined period of larval development [8].
• In addition to mutations in sup-20, other mutations causing muscle defects, such as unc-54 and unc-22 mutations, suppress the hypercontracted phenotype of unc-105 [14].
• The six proteins also cosedimented with thick filaments purified by gradient centrifugation from CB190 mutants lacking myosin heavy chain B and from CB1214 mutants lacking paramyosin [15].

Analytical, diagnostic and therapeutic context of unc-54

• We have designed genetic techniques that select directly for unc-54 mutants [7].
• Sequence analysis of mutations that affect the synthesis, assembly and enzymatic activity of the unc-54 myosin heavy chain of Caenorhabditis elegans [16].
• The properties of a small internal deletion mutant, E675, have been exploited in the molecular cloning of the unc-54 gene [17].
• We describe the dissection of a body muscle-specific enhancer sequence contained within the Caenorhabditis elegans myosin heavy chain gene unc-54 [18].

References