Rhythmic serotonin N-acetyltransferase mRNA degradation is essential for the maintenance of its circadian oscillation.
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.
Kim
Tae-Don
TD
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
JS
Kim
Jong Heon
JH
Myung
Jihwan
J
Chae
Hee-Don
HD
Woo
Kyung-Chul
KC
Jang
Sung Key
SK
Koh
Duk-Su
DS
Kim
Kyong-Tai
KT
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D010870:Pineal Gland / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D051381:Rats
D020413:3' Untranslated Regions; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D047068:Arylalkylamine N-Acetyltransferase