Rhythmic control of AANAT translation by hnRNP Q in circadian melatonin production.
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.
Kim
Tae-Don
TD
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.
Woo
Kyung-Chul
KC
Cho
Sungchan
S
Ha
Dae-Cheong
DC
Jang
Sung Key
SK
Kim
Kyong-Tai
KT
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
D020121:5' Untranslated Regions; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; C520223:Aanat protein, rat; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin