Rhythmic serotonin N-acetyltransferase mRNA degradation is essential for the maintenance of its circadian oscillation

T.-D. Kim, J.-S. Kim, H.K. Jong, J. Myung, H.-D. Chae, K.-C. Woo, K.J. Sung, D.-S. Koh, K.-T. Kim

研究成果: 雜誌貢獻文章同行評審

67 引文 斯高帕斯(Scopus)

摘要

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase [AANAT]) is the key enzyme in melatonin synthesis regulated by circadian rhythm. To date, our understanding of the oscillatory mechanism of melatonin has been limited to autoregulatory transcriptional and posttranslational regulations of AANAT mRNA. In this study, we identify three proteins from pineal glands that associate with cis-acting elements within species-specific AANAT 3′ untranslated regions to mediate mRNA degradation. These proteins include heterogeneous nuclear ribonucleoprotein R (hnRNP R), hnRNP Q, and hnRNP L. Their RNA-destabilizing function was determined by RNA interference and overexpression approaches. Expression patterns of these factors in pineal glands display robust circadian rhythm. The enhanced levels detected after midnight correlate with an abrupt decline in AANAT mRNA level. A mathematical model for the AANAT mRNA profile and its experimental evidence with rat pinealocytes indicates that rhythmic AANAT mRNA degradation mediated by hnRNP R, hnRNP Q, and hnRNP L is a key process in the regulation of its circadian oscillation. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
原文英語
頁(從 - 到)3232-3246
頁數15
期刊Molecular and Cellular Biology
25
發行號8
DOIs
出版狀態已發佈 - 2005
對外發佈

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