Splicing of Juvenile and Adult Tau mRNA Variants is Regulated by Thyroid Hormone

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 88; no. 9; pp. 4035 - 4039
• Main Authors: ANIELLO, F, COUCHIE, D, BRIDOUX, A.-M, GRIPOIS, D, NUNEZ, J
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-05-1991; National Acad Sciences
• Subjects: Animals; Base Sequence; Biological and medical sciences; Blotting, Northern; Brain - growth & development; Brain - physiology; Cerebellum; Cerebral hemispheres; Developmental biology; Fundamental and applied biological sciences. Psychology; Gene Expression; Hypothyroidism - genetics; Messenger RNA; Microtubule-Associated Proteins - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Neurons; Nucleic Acid Hybridization; Oligonucleotides - chemistry; Polymerase Chain Reaction; Purkinje cells; Rats; RNA; RNA probes; RNA Splicing; RNA, Messenger - genetics; Splicing; tau Proteins; Thyroid hormones; Thyroid Hormones - physiology; Brain; Splicing; Rat; In situ; Genetic variant; Rodentia; Gene expression; Postnatal development; Northern blotting; Vertebrata; Regulation(control); Mammalia; Messenger RNA; Thyroid hormone; Protection test
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.9.4035

The effect of thyroid hormone on the expression of tau transcripts was studied during postnatal brain development. The level of tau mRNA was only slightly changed postnatally in the cerebral hemispheres of hypothyroid rats, whereas the level of tau mRNA in the cerebellum was maintained at a higher level than in the euthyroid controls. As shown by in situ hybridization studies, such an alteration in tau mRNA expression can be ascribed to an effect of thyroid hormone on the rate of migration of the granule cells in the cerebellum; that tau mRNAs remain high in the cerebellum as long as the granule cells are migrating correlates with the observation that hypothyroidism slows the rate of migration of granule cells. RNase protection assays also showed that thyroid hormone deficiency delays the transition between the immature and mature tau transcripts in both brain regions. Thus, one of the effects of thyroid hormone is to regulate the splicing mechanism that allows replacement of the juvenile tau variants by the adult entities during neuronal differentiation.