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PMID: 11046130 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cloning and characterization of two novel thyroid hormone receptor beta isoforms.

Molecular and cellular biology ·Vol. 20 ·No. 22 ·2000-11-00 ·Pages 8329-42

Williams GR

Abstract

Thyroid hormone (T(3)) activates nuclear receptor transcription factors, encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) genes, to regulate target gene expression. Several TR isoforms exist, and studies of null mice have identified some unique functions for individual TR variants, although considerable redundancy occurs, raising questions about the specificity of T(3) action. Thus, it is not known how diverse T(3) actions are regulated in target tissues that express multiple receptor variants. I have identified two novel TRbeta isoforms that are expressed widely and result from alternative mRNA splicing. TRbeta3 is a 44.6-kDa protein that contains an unique 23-amino-acid N terminus and acts as a functional receptor. TRDeltabeta3 is a 32.8-kDa protein that lacks a DNA binding domain but retains ligand binding activity and is a potent dominant-negative antagonist. The relative concentrations of beta3 and Deltabeta3 mRNAs vary between tissues and with changes in thyroid status, indicating that alternative splicing is tissue specific and T(3) regulated. These data provide novel insights into the mechanisms of T(3) action and define a new level of specificity that may regulate thyroid status in tissue.

MeSH Terms
5' Untranslated Regions Alternative Splicing Animals Binding Sites Blotting, Northern Cloning, Molecular DNA/metabolism Male Molecular Sequence Data Organ Specificity Protein Isoforms/genetics,metabolism RNA, Messenger Rats Rats, Sprague-Dawley Receptors, Thyroid Hormone/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Response Elements Transcription Factors/metabolism Triiodothyronine/metabolism
Chemicals
5' Untranslated Regions Protein Isoforms RNA, Messenger Receptors, Thyroid Hormone Recombinant Fusion Proteins Transcription Factors Triiodothyronine DNA
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Williams G R
ICSM Molecular Endocrinology Group, Division of Medicine and MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 ONN, United Kingdom. graham.williams@ic.ac.uk
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.22.8329-8342.2000
Email
graham.williams@ic.ac.uk
Published
2000-11-00
Pages
8329-42
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC102140
Subset
IM
Grants
Wellcome Trust · United Kingdom
Databases
GENBANK
AF239914, AF239915, AF239916
External Links
PubMed source DOI: 10.1128/MCB.20.22.8329-8342.2000 PMC Full Text View journal details
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