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Null mutations of the Caenorhabditis elegans unc-22 gene cause a pronounced body
surface twitch associated with impaired movement and disruption of muscle
structure. 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. This paper reports additional DNA sequence information that has
revealed the transcription start of unc-22, the N terminus of twitchin, and an
explanation for the weak phenotype of a transposon insertion allele. These new
data indicate that the unc-22 gene is 18 kb larger than previously reported and
has a transcription unit of 38,308 bp. These data add 791 amino acids to the
twitchin N terminus for a complete polypeptide size of 6,839 amino acids and a
predicted molecular weight of 753,494. This new polypeptide sequence includes
four additional copies of the above-mentioned immunoglobulin-like domains and
also includes a glycine-rich sequence that might form a flexible hinge. The
additional coding sequence reveals that the insertion of the Tc1 transposon, in
the unc-22 allele, st139, should disrupt twitchin structure because it is
located in an exon. However, cDNA sequencing has revealed that several cryptic
splice donors and acceptors adjacent to the Tc1 insertion site are used to
splice the transposon out of unc-22(st139) mRNA. One of these splicing events
produces a near wild-type mRNA that deletes only six amino acids from twitchin,
and this might explain the unusually mild phenotype associated with this
mutation.
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