title: Heterogeneous ribonucleoprotein R regulates arylalkylamine N-acetyltransferase synthesis via internal ribosomal entry site-mediated translation in a circadian manner.
abstract: Rhythmic arylalkylamine N-acetyltransferase (AANAT) synthesis is a prominent circadian-controlled response that occurs in most mammals. AANAT is the core enzyme in melatonin production; because melatonin participates in many physiological processes, the regulation of AANAT is an important research topic. In this study, we focused on the role of heterogeneous ribonucleoprotein R (hnRNP R) in the translation of AANAT. A novel RNA-binding protein hnRNP R widely interacted with the 5' untranslated region (UTR) of AANAT mRNA and contributed to translation through an internal ribosomal entry site (IRES). Fine-tuning of AANAT protein synthesis occurred in response to knockdown and overexpression of hnRNP R. Nocturnal elevation of AANAT protein was dependent on the rhythmic changes of hnRNP R, whose levels are elevated in the pineal gland during nighttime. Increases in hnRNP R additionally improved AANAT production in rat pinealocytes under norepinephrine (NE) treatment. These results suggest that cap-independent translation of AANAT mRNA plays a role in the rhythmic synthesis of melatonin through the recruitment of translational machinery to hnRNP R-bound AANAT mRNA.
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.
authors.forename: Hwa-Rim
authors.initials: HR
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.|Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Korea.
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.
authors.forename: Youngseob
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.|Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Kyung-Ha
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.|Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Do-Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.|Newlife Cosmetics R&D Center for Skin Science, Gyeongsansi, Gyeongbuk, Korea.
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Woo
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.|Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.|Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D007150:Immunohistochemistry; D000067556:Internal Ribosome Entry Sites / Q000235:genetics; D008550:Melatonin / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012261:Ribonucleoproteins / Q000378:metabolism
chemical_list: D000067556:Internal Ribosome Entry Sites; D012261:Ribonucleoproteins; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin; D009638:Norepinephrine
keywords: arylalkylamine N-acetyltransferase; circadian rhythm; heterogeneous ribonucleoprotein R; internal ribosomal entry site-mediated translation; pineal gland