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GENES & DEVELOPMENT 21:797-810, 2007
©2007 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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Rhythmic control of AANAT translation by hnRNP Q in circadian melatonin production

Tae-Don Kim, Kyung-Chul Woo, Sungchan Cho, Dae-Cheong Ha, Sung Key Jang, and Kyong-Tai Kim1

Department of Life Science, Division of Molecular and Life Sciences, Systems Bio-Dynamics NCRC, Pohang University of Science and Technology, Pohang, Kyung-Buk 790-784, Republic of Korea

The circadian rhythm of pineal melatonin requires the nocturnal increment of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase [AANAT]) protein. To date, only limited information is available in the critical issue of how AANAT protein expression is up-regulated exclusively at night regardless of its species-specific mRNA profiles. Here we show that the circadian timing of AANAT protein expression is regulated by rhythmic translation of AANAT mRNA. This rhythmic control is mediated by both a highly conserved IRES (internal ribosome entry site) element within the AANAT 5' untranslated region and its partner hnRNP Q (heterogeneous nuclear ribonucleoprotein Q) with a peak in the middle of the night. Consistent with the enhancing role of hnRNP Q in AANAT IRES activities, knockdown of the hnRNP Q level elicited a dramatic decrease of peak amplitude in the AANAT protein profile parallel to reduced melatonin production in pinealocytes. This translational regulation of AANAT mRNA provides a novel aspect for achieving the circadian rhythmicity of vertebrate melatonin.

[Keywords: AANAT; translation; IRES; hnRNP Q; melatonin; circadian rhythm]

Received November 30, 2006; revised version accepted February 20, 2007.

1 Corresponding author.

E-MAIL ktk{at}postech.ac.kr; FAX 82-54-279-2199.

Supplemental Material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1519507


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