Key result
Both the small alternatively spliced TK mRNA and the large TK mRNA were equally dependent on the replicative state of the cell, indicating the spliced intron does not allow persistence in postreplicative cells.
The alternatively spliced small TK mRNA remains dependent on the replicative state of the cell, similar to the large TK mRNA.
Alternative splicing of TK 3' UTR may diversify transcript regulation; leaves open isoform-specific functional effects.
The nucleotide sequence of independent cDNA clones revealed that TK transcripts can undergo alternative splicing within the 3' nontranslated portion of the message. The most abundant mRNA is 2.1 kb in length and is colinear with the underlying genomic sequence for at least the first 1052 bases of its 3' nontranslated region. A less abundant mRNA, 1.3 kb in length, differs from the larger mRNA in that an 863 base intron is spliced from the 3' nontranslated region. The possibility that removal of the alternatively spliced intron allows the small mRNA to persist in postreplicative cells was investigated in two ways. First, the levels of large and small TK mRNA in tissues expressing differential growth rates was determined. Second, the pattern of TK enzyme expression during differentiation was analyzed in muscle cells transformed with recombinant TK genes lacking the 3' nontranslated intron. Both lines of experimentation indicated that the small TK mRNA was as dependent as the large TK mRNA on the replicative state of the cell.
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Merrill et al. (1986) studied this question. Alternative splicing of an 863 base intron from the 3' nontranslated region of TK mRNA vs. Large TK mRNA (colinear with genomic sequence) was evaluated on Dependence on the replicative state of the cell. Both the small alternatively spliced TK mRNA and the large TK mRNA were equally dependent on the replicative state of the cell, indicating the spliced intron does not allow persistence in postreplicative cells.
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