Serotonin 2C Receptor as a Superhero: Diversities and Talents in the RNA Universe for Editing, Variant, Small RNA and Other Expected Functional RNAs

Abstract

The serotonin 2C receptor subtype (5-HT2C) seems to have various physiological roles in addition to the function of the receptor. The serotonin receptors are classified into many subtypes (1), especially more than 10 splicing variants have been reported for the 5-HT4 subtype (1, 2), which has been recently reported to be involved in the circadian clock (3, 4). Among the various serotonin receptor subtypes, 5-HT2C is especially interesting. The history of studies on 5-HT2C can also convey its distinct personality. We are often surprised and puzzled by novel discoveries about 5-HT2C. In this review, the "curriculum vitae" of 5-HT2C is first introduced, followed by a discussion of the unique world of 5-HT2C, including RNA editing, short variants, relationship with small RNA, therapeutic potential for functional mental disease (FMD) such as depression and schizophrenia, and the "friendship" with Wakan-yaku (Sino-Japanese traditional medicine). Curriculum vitae of 5-HT2C5-HT2C was previously named 5-HT 1C . Therefore, searches for papers about the receptor written before 1992 must use "5-HT 1C " as the keyword. The serotonin receptor was previously classified into 5-HT 1 and 5-HT 2 by the receptor's affinity for serotonin; 5-HT 1 has approximately 100 times greater affinity for serotonin than does 5-HT 2 . This is caused by the historical background when the "receptor binding assay" was the mainstream method of receptor studies. Each receptor subtype was further subdivided by drug affinities. Thereafter, when the mainstream experimental techniques shifted to second messenger systems, it was clarified that the 5-HT 1 group is coupled to the cAMP system and that the 5-HT 2 group is linked with the inositolphosphate turnover system. However, one subtype of 5-HT 1 did not fulfill this classification: 5-HT 1C . Therefore, with the approval of all scientists, 5-HT 1C was transferred to the 5-HT 2 family and renamed 5-HT2C (5).When this receptor was still called 5-HT 1C , receptor cloning was performed by the "functional cloning method" using Xenopus oocytes injected with an RNA library followed by electrophysiological detection. 13, 2014; Accepted October 13, 2014 Abstract. The serotonin 2C receptor subtype (5-HT2C) has a unique profession and continues to provide exciting and critical new information. The 5-HT2C is modulated at the RNA level by several mechanisms, including editing, short variant generation, and small RNAs. Recently, these phenomena, which had been demonstrated individually, were shown to be associated with each other. At present, many reports provide information about the influence of RNA regulation on receptor protein activities and expression, which was thought to be the final functional product. However, complicated behavior at the RNA stage allows us to imagine that the RNA itself has functional roles in the RNA universe. The 5-HT2C RNA may play several roles. This review will outline previous 5-HT2C studies and prospects for future studies.

MRI detection of the activated region in the rat brain by Hochuekki-to, a traditional oriental medicine, and the related expression of BNIP-3 mRNA, a candidate of depression-related factor

“…We also found that HET is involved serotonin 2C receptor (5-HT2CR) function and the mRNA expression [2] as well as antidepressants [2][3][4]. 5-HT2CR has been reportedly suggested the concerning with the neuronal development [5][6][7]. It has been also reported that HET-or typical antidepressants-treatment strongly enhanced BNIP-3 mRNA expression in cloned neuronal cells by experiments starting from the results of DNA array [8].…”

RNA Editing of Serotonin 2C Receptor and Alcohol Intake

“…To date, ADAR1, ADAR2, and ADAR3 have been identified, whereas target RNAs of ADAR3 have not been found (Nishikura, 2010). RNA is an energetically unstable molecule, thus it is considered that RNA is edited in order to respond rapidly to a change in the surrounding environment (Tohda, 2014). Most RNA editing occurs in 3 or 5 untranslated regions and this regulates gene expression.…”