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Involvement of AU‐rich RNA Binding Proteins in the Thyroid Hormone Induced Increase in Hepatic HMG‐CoA Reductase Expression
Author(s) -
Ness Gene Charles,
Dimas Angela,
Brooks Patricia A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.705.3
Enhanced expression of hepatic HMG‐CoA reductase (HMGR) promoted by thyroid hormone involves RNA stabilization. T 3 has been shown to increase the half‐life of hepatic HMGR mRNA by nearly 5‐fold. Since the 3′ untranslated region of HMGR mRNA contains several AU‐rich elements (ARE), we investigated whether AU‐rich RNA binding proteins might be involved. Western blotting analysis of liver microsomes and cytosol from hypophysectomized rats treated with or without T 3 was performed. T 3 treatment essentially eliminated tristetraprolin (TTP) from microsomes but not from cytosol. Hepatic TTP mRNA levels were reduced by T 3 treatment. TTP plays a central role in accelerating the decay of ARE containing mRNAs. A+U‐rich element‐binding factor 1 (AUF‐1) was increased markedly by T 3 treatment in both liver microsomes and cytosol. This protein acts to stabilize ARE containing mRNAs. Also HUR protein levels were increased by T 3 treatment. AUF‐1 and HUR mRNA levels were not significantly affected by T 3 treatment, indicating a posttranscription mode of regulation. AUH levels were unaffected. T‐cell intracellular antigen‐1(TIA‐1) was dramatically increased in both microsomes and cytosol. This protein has been reported to be involved in translational repression, alternative splicing, promoting apoptosis, enhancing mRNA decay and formation of stress granules. Its role in liver is not known. The changes in hepatic TTP, AUF‐1, and HUR protein levels are consistent with T 3 acting to stabilize hepatic HMGR mRNA. This investigation was supported grant DK075414 from NIH.