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PMID: 15798208 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular and cellular biology ·Vol. 25 ·No. 8 ·2005-04-00 ·Pages 3232-46

Kim TD, Kim JS, Kim JH, Myung J, Chae HD, Woo KC, Jang SK, Koh DS, Kim KT

Abstract

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.

MeSH Terms
3' Untranslated Regions/metabolism Animals Arylalkylamine N-Acetyltransferase/genetics,metabolism Base Sequence Circadian Rhythm/genetics,physiology Heterogeneous-Nuclear Ribonucleoproteins/genetics,metabolism,physiology Molecular Sequence Data Pineal Gland/metabolism RNA Stability RNA, Messenger/metabolism RNA, Small Interfering/genetics,pharmacology RNA-Binding Proteins/metabolism,physiology Rats
Chemicals
3' Untranslated Regions Heterogeneous-Nuclear Ribonucleoproteins RNA, Messenger RNA, Small Interfering RNA-Binding Proteins Arylalkylamine N-Acetyltransferase
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kim Tae-Don
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.
Kim Jong-So
Kim Jong Heon
Myung Jihwan
Chae Hee-Don
Woo Kyung-Chul
Jang Sung Key
Koh Duk-Su
Kim Kyong-Tai
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.8.3232-3246.2005
Published
2005-04-00
Pages
3232-46
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1069600
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.25.8.3232-3246.2005 PMC Full Text View journal details
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