title: Rhythmic control of AANAT translation by hnRNP Q in circadian melatonin production.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Woo
authors.forename: Sungchan
authors.initials: S
authors.lastname: Cho
authors.forename: Dae-Cheong
authors.initials: DC
authors.lastname: Ha
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D020121:5' Untranslated Regions / Q000378:metabolism; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002940:Circadian Rhythm / Q000502:physiology*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D008550:Melatonin / Q000096:biosynthesis*; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010870:Pineal Gland / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012756:Sheep
chemical_list: D020121:5' Untranslated Regions; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; C520223:Aanat protein, rat; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin