Regulation of tau RNA maturation by thyroid hormone is mediated by the neural RNA-binding protein musashi-1

Ana Cuadrado, Luis F. García-Fernández, Takao Imai, Hideyuki Okano, Alberto Muñoz

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The tau gene encodes a microtubule-associated protein expressed by neuronal and glial cells. Abnormal deposits of Tau protein are characteristic of several neurodegenerative disorders. Additionally, mutations affecting tau pre-mRNA alternative splicing of exon 10 are associated with frontotemporal dementia and Parkinsonism linked to chromosome 17. In rodents, this process is developmentally regulated by thyroid hormone (T3) causing the predominance of exon 10-containing transcripts. Here we demonstrate that musashi-1 (msi-1) gene is induced by T3 during rat brain development and in N2a cells. T3 increases msi-1 mRNA level in an actinomycin D-sensitive, cycloheximide-resistant fashion without affecting its half-life, which suggests a transcriptional effect. Both ectopic Msi-1 expression and T3 treatment increased the proportion of exon 10-containing tau transcripts. Furthermore, antisense msi-1 expression inhibited T3 action. Our results show that msi-1 mediates the posttranscriptional regulation of tau expression by T3.

Original languageEnglish
Pages (from-to)198-210
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume20
Issue number2
DOIs
Publication statusPublished - 2002

Fingerprint

RNA-Binding Proteins
Thyroid Hormones
Exons
RNA
tau Proteins
Frontotemporal Dementia
Chromosomes, Human, Pair 17
Microtubule-Associated Proteins
RNA Precursors
Alternative Splicing
Dactinomycin
Triiodothyronine
Cycloheximide
Neuroglia
Neurodegenerative Diseases
Genes
Half-Life
Rodentia
Messenger RNA
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Regulation of tau RNA maturation by thyroid hormone is mediated by the neural RNA-binding protein musashi-1. / Cuadrado, Ana; García-Fernández, Luis F.; Imai, Takao; Okano, Hideyuki; Muñoz, Alberto.

In: Molecular and Cellular Neuroscience, Vol. 20, No. 2, 2002, p. 198-210.

Research output: Contribution to journalArticle

Cuadrado, Ana ; García-Fernández, Luis F. ; Imai, Takao ; Okano, Hideyuki ; Muñoz, Alberto. / Regulation of tau RNA maturation by thyroid hormone is mediated by the neural RNA-binding protein musashi-1. In: Molecular and Cellular Neuroscience. 2002 ; Vol. 20, No. 2. pp. 198-210.
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