Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2005;9(3):143-9.
doi: 10.1007/BF03260082.

Nonsense-associated alternative splicing of the human thyroglobulin gene

Affiliations

Nonsense-associated alternative splicing of the human thyroglobulin gene

Fernando M Mendive et al. Mol Diagn. 2005.

Abstract

Introduction: We have described in previous articles a nonsense mutation (4588C>T, R1511X) in exon 22 of the thyroglobulin (TG) gene in a member of a family with a complex history of congenital goiter. In the mutated thyroid gland, full-length thyroglobulin mRNA is almost undetectable. However, a smaller transcript is detected in which the mutated exon 22 is skipped and the reading frame restored. It is conceivable that alternative splicing might be a mechanism involved in the rescue of nonsense mutations.

Methods: To investigate whether the detection of the alternative mRNA is due to an increase in its concentration or its preferential amplification during reverse transcriptase-PCR in the absence of the normal full-length mRNA competitor, we set up an assay in which the competitor mRNA was provided. We also studied the effect of the 4588C>T mutation on exon definition and processing using wild-type and mutated minigenes.

Results: The detection of the alternative mRNA lacking exon 22 is not caused by the absence of the full-length competitor. In contrast, our results demonstrate that the alternative transcript preferentially accumulates in the mutated thyroid at a level similar to the full-length transcript in control tissue. Transient expression experiments with wild-type and mutated minigenes indicate that the mutated exon is as efficiently spliced as the wild-type, suggesting that the 4588C>T mutation does not interfere with exon 22 definition and processing.

Conclusions: The alternative splicing of the TG gene described in this article constitutes a new case of nonsense-associated alternative splicing. We have shown that the mutation itself does not interfere with exon definition and processing in vitro. Our results support the hypothesis that the alternative splicing of the mutated exon is driven by the interruption of the reading frame.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Thyroid. 2001 Jul;11(7):685-90 - PubMed
    1. J Clin Endocrinol Metab. 1999 Apr;84(4):1438-44 - PubMed
    1. Thyroid. 1998 Apr;8(4):291-7 - PubMed
    1. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5598-603 - PubMed
    1. J Clin Endocrinol Metab. 1999 Jul;84(7):2537-42 - PubMed

Publication types

Associated data

LinkOut - more resources