Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 275, Issue 15, Pages 11507-11513Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.275.15.11507
Keywords
-
Categories
Funding
- NIDDK NIH HHS [DK 48034, DK45586] Funding Source: Medline
- NIGMS NIH HHS [GM 55922] Funding Source: Medline
Ask authors/readers for more resources
Thyroid hormone (T-3) coordinates growth, differentiation, and metabolism by binding to nuclear thyroid hormone receptors (TRs), The TR alpha gene encodes T-3-activated TR alpha 1 (NR1Ala) as well as an antagonistic, non-T-3-binding alternatively spliced product, TR alpha 2 (NR1Alb). Thus, the TR alpha 1/TR alpha 2 ratio is a critical determinant of T-3 action. However, the mechanisms underlying this post-transcriptional regulation are unknown. We have identified a non-consensus, TR alpha 2-specific 5' splice site and conserved intronic sequences as key determinants of TR alpha mRNA processing. In addition to these cis-acting elements, a novel regulatory feature is the orphan receptor RevErbA alpha (NR1D1) gene, which is transcribed from the opposite direction at the same locus and overlaps the TR alpha 2 coding region. RevErbA alpha gene expression correlates with a high TR alpha 1/TR alpha 2 ratio in a number of tissues. Here we demonstrate that coexpression of RevErbA alpha and TR alpha regulates the TR alpha 1/TR alpha 2 ratio in intact cells. Thus, both cis- and trans-regulatory mechanisms contribute to cell-specific post-transcriptional regulation of TR gene expression and T-3 action.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available