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Molecular and Cellular Biology, April 2005, p. 3232-3246, Vol. 25, No. 8
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.8.3232-3246.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Rhythmic Serotonin N-Acetyltransferase mRNA Degradation Is Essential for the Maintenance of Its Circadian Oscillation

Tae-Don Kim,1 Jong-So Kim,1 Jong Heon Kim,1 Jihwan Myung,2 Hee-Don Chae,1 Kyung-Chul Woo,1 Sung Key Jang,1 Duk-Su Koh,2 and Kyong-Tai Kim1*

Department of Life Science,1 Department of Physics, Pohang University of Science and Technology, Pohang, Kyung-Buk, Republic of Korea2

Received 6 September 2004/ Returned for modification 5 October 2004/ Accepted 23 December 2004

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.

* Corresponding author. Mailing address: National Research Laboratory, Department of Life Science, Pohang University of Science and Technology, San 31 Hyoja-Dong, Pohang, Kyung-Buk 790-784, Republic of Korea. Phone: 82 54 279 2297. Fax: 82 54 279 2199. E-mail: ktk{at}postech.ac.kr.

Molecular and Cellular Biology, April 2005, p. 3232-3246, Vol. 25, No. 8
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.8.3232-3246.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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