Heterogeneous ribonucleoprotein R regulates arylalkylamine N ‐acetyltransferase synthesis via internal ribosomal entry site‐mediated translation in a circadian manner

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 (hn RNP R) in the translation of AANAT . A novel RNA ‐binding protein hn RNP R widely interacted with the 5′ untranslated region ( UTR ) of AANAT m RNA 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 hn RNP R . Nocturnal elevation of AANAT protein was dependent on the rhythmic changes of hn RNP R , whose levels are elevated in the pineal gland during nighttime. Increases in hn RNP R additionally improved AANAT production in rat pinealocytes under norepinephrine ( NE ) treatment. These results suggest that cap‐independent translation of AANAT m RNA plays a role in the rhythmic synthesis of melatonin through the recruitment of translational machinery to hn RNP R ‐bound AANAT m RNA .