Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Jan;75(1):74–78. doi: 10.1073/pnas.75.1.74

Abnormal cellular localization of thyroglobulin mRNA associated with hereditary congenital goiter and thyroglobulin deficiency.

W F Van Voorthuizen, C Dinsart, R A Flavell, J J DeVijlder, G Vassart
PMCID: PMC411186  PMID: 272675

Abstract

The goiters in a breed of hypothyroid goats contain only minute amounts of thyroblobulin-related antigens (0.01% of normal value). We have analyzed these goiters for the presence of mRNA coding for thyroglobulin. Using DNA complementary to beef 33S thyroglobulin mRNA as a probe, we found that the mRNA sequence is present in the goat goiter but at a concentration 1/10-1/40 that of normal goat thyroid. Hybrids of cDNA with either goiter or normal thyroid RNA exhibited identical sharp melting curves which suggests that the same RNA sequence is responsible for hybridization in both tissues. Normal goat thyroid contains a population of large membrane-bound polysomes engaged in throglobulin synthesis. In contrast, such polysomes are absent in the goiter. In regard to subcellular distribution, the relative amount of the thyroglobulin mRNA sequences from the goiter in nuclear RNA was 42% of normal, in cytoplasmic RNA was 7% of normal, and in the membrane fraction was only 1-2% of normal. Our results suggest that the lack of thyroglobulin in these goiters is due to a defect in thyroglobulin mRNA which leads to aberrant processing and/or transport of it from its site of synthesis to the endoplasmic reticulum.

Full text

PDF
74

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Davies E., Dumont J. E., Vassart G. Improved techniques for the isolation of intact thyroglobulin-synthesizing polysomes. Anal Biochem. 1977 May 15;80(1):289–297. doi: 10.1016/0003-2697(77)90647-9. [DOI] [PubMed] [Google Scholar]
  2. Dinsart C., Van Voorthuizen F., Vassart G. Reverse transcription of thyroglobulin 33-S mRNA. Eur J Biochem. 1977 Aug 15;78(1):175–181. doi: 10.1111/j.1432-1033.1977.tb11727.x. [DOI] [PubMed] [Google Scholar]
  3. Kan Y. W., Holland J. P., Dozy A. M., Varmus H. E. Demonstration of non-functional beta-globin mRNA in homozygous beta (0) thalassemia. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5140–5144. doi: 10.1073/pnas.72.12.5140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Lecocq R. E., Dumont J. E. In vivo and in vitro effects of thyrotropin on ribosomal pattern of dog thyroid. Biochim Biophys Acta. 1973 Mar 19;299(2):304–311. doi: 10.1016/0005-2787(73)90354-7. [DOI] [PubMed] [Google Scholar]
  5. Lissitzky S., Bismuth J., Jaquet P., Castay M., Michel-Béchet M., Koutras D. A., Pharmakiotis A. D., Moschos A., Psarras A., Malamos B. Congenital goiter with impaired thyroglobulin synthesis. J Clin Endocrinol Metab. 1973 Jan;36(1):17–29. doi: 10.1210/jcem-36-1-17. [DOI] [PubMed] [Google Scholar]
  6. Riesco G., Bernal J., Sanchez-Franco F. Thyroglobulin defect in a human congenital goiter. J Clin Endocrinol Metab. 1974 Jan;38(1):33–41. doi: 10.1210/jcem-38-1-33. [DOI] [PubMed] [Google Scholar]
  7. Rijnberk A., De Vijlder J. J., Van Dijk J. E., Jorna T. J., Tegelaers W. H. Congenital defect in iodothyronine synthesis. Clinical aspects of iodine metabolism in goats with congenital goitre and hypothyroidism. Br Vet J. 1977 Sep-Oct;133(5):495–503. doi: 10.1016/s0007-1935(17)33992-1. [DOI] [PubMed] [Google Scholar]
  8. Vassart G., Brocas H., Lecocq R., Dumont J. E. Thyroglobulin messenger RNA: translation of a 33-S mRNA into a peptide immunologically related to thyroglobulin. Eur J Biochem. 1975 Jun 16;55(1):15–22. doi: 10.1111/j.1432-1033.1975.tb02133.x. [DOI] [PubMed] [Google Scholar]
  9. Vassart G., Dumont J. E. Identification of polysomes synthesizing thyroglobulin. Eur J Biochem. 1973 Jan 15;32(2):322–330. doi: 10.1111/j.1432-1033.1973.tb02613.x. [DOI] [PubMed] [Google Scholar]
  10. Vassart G., Refetoff S., Brocas H., Dinsart C., Dumont J. E. Translation of thyroglobulin 33S messenger RNA as a means of determining thyroglobulin quaternary structure. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3839–3843. doi: 10.1073/pnas.72.10.3839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Vassart G. Specific synthesis of thyroglobulin on membrane bound thyroid ribosomes. FEBS Lett. 1972 Apr 15;22(1):53–56. doi: 10.1016/0014-5793(72)80217-5. [DOI] [PubMed] [Google Scholar]
  12. Wetmur J. G., Davidson N. Kinetics of renaturation of DNA. J Mol Biol. 1968 Feb 14;31(3):349–370. doi: 10.1016/0022-2836(68)90414-2. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES