Kp. Menon et Ef. Neufeld, EVIDENCE FOR DEGRADATION OF MESSENGER-RNA ENCODING ALPHA-L-IDURONIDASE IN HURLER FIBROBLAST WITH PREMATURE TERMINATION ALLELES, Cellular and molecular biology, 40(7), 1994, pp. 999-1005
Mutations in the gene encoding alpha-L-iduronidase (IDUA) are the caus
e of Hurler syndrome. Fibroblasts from patients homozygous for nonsens
e IDUA alleles have much reduced mRNA detectable by Northern analysis,
as has been observed in many other instances of premature translation
termination. Yet RT-PCR (reverse transcription followed by PCR amplif
ication) showed a normal level of a segment covering exons 1 and 2 in
Hurler cells homozygous for alleles bearing the nonsense mutations, Q7
0X or W402X. The 3' end of the segment was between exons 2 and 4. The
results indicate that the nonsense RNA was degraded to fragment(s), in
dependent of the position of the mutation (exon 2 or exon 9, respectiv
ely). Treatment of the cells with cycloheximide resulted in some incre
ase of intact mRNA, suggesting that translation is required for mRNA d
egradation.