RBM8A (Y14) contains an RNA-binding motif and forms a tight heterodimer with Magoh. The heterodimer is known to be a member of the exon junction complex that forms on mRNA before export and it is required for mRNA metabolism processes such as splicing, mRNA export and nonsense-mediated mRNA decay. Recently, deficient cellular proliferation has been observed in RBM8A- or Magoh-depleted cells. These results prompted us to study the role of RBM8A in cell cycle progression of human tumour cells. The depletion of RBM8A in A549 cells resulted in poor cell survival and the accumulation of mitotic cells. After release from G1/S arrest induced by a double thymidine block, the RBM8A-silenced cells could not proceed to the next G1 phase beyond G2/M phase. Finally, the sub-G1 population increased and the apoptosis markers caspases 3/7 were activated. Silenced cells exhibited an increased frequency of multipolar or monopolar centrosomes, which may have caused the observed deficiency in cell cycle progression. Finally, silencing of either RBM8A or Magoh resulted in mutual downregulation of the other protein. These results illustrate that the RBM8A-Magoh mRNA binding complex is required for M phase progression and both proteins may be novel targets for anticancer therapy.

Peanut skin (Arachis hypogaea L., Fabaceae) is an abundant source for polyphenols, such as proanthocyanidin oligomers. To determine whether proanthocyanidin has beneficial effects on skin, we tested for inhibitory activity of proanthocyanidins isolated from peanut skin on inflammatory cytokine production and melanin synthesis in cultured cell lines. Administration of peanut skin extract (PSE, 200 µg/mL) decreased melanogenesis in cultured human melanoma HMV-II co-stimulated with phorbol-12-myristate-13-acetate. It also decreased production of inflammatory cytokines (PSE at 100 µg/mL), tumor necrosis factor-α and interleukin-6, in cultured human monocytic THP-1 cells in response to lipopolysaccharide. We isolated ten known proanthocyanidins and one new proanthocyanidin trimer from the PSE. The structure of the new compound (5) was determined by 1D- and 2D-NMR and mass spectrometry analyses, and was determined as epicatechin-(2β→O→7,4β→6)-epicatechin-(4β→6)-epicatechin. The other known proanthocyanidins were identified as proanthocyanidin monomers (1), dimers (6-9), trimers (3-5) and tetramers (2, 10, 11). They showed suppressive activities against melanogenesis and cytokine production at concentrations ranging from 0.1-10 µg/mL. Among the tested compounds, suppressive activities of proanthocyanidin dimers or trimers in two assay systems were stronger than those obtained with monomer or tetramers. These data indicate that proanthocyanidin oligomers from peanut skin have the potential to reduce dermatological conditions such as inflammation and melanogenesis.

RBM8A (Y14) is carrying RNA-binding motif and forms the tight heterodimer with MAGOH. The heterodimer is known to be a member of exon junction complex on exporting mRNA and is required for mRNA metabolisms such as splicing, mRNA export and nonsense-mediated mRNA decay. Almost all RBM8A-MAGOH complexes localize in nucleoplasm and shuttle between nuclei and cytoplasm for RNA metabolism. Recently, the abnormality of G2/M transition and aberrant centrosome regulation in RBM8A- or MAGOH-deficient cells has been reported. These results prompt us to the reevaluation of the localization of RBM8A-MAGOH in human cells. Interestingly, our immunostaining experiments showed the localization of these proteins in centrosome in addition to nuclei. Furthermore, the transiently expressed eYFP-tagged RBM8A and Flag-tagged MAGOH also co-localized with centrosome signals. In addition, the proximity ligation in situ assay was performed to detect the complex formation in centrosome. Our experiments clearly showed that Myc-tagged RBM8A and Flag-tagged MAGOH formed a complex in centrosome. GFP-tagged PLK1 also co-localized with Myc-RBM8A. Our results show that RBM8A-MAGOH complex is required for M-phase progression via direct localization to centrosome rather than indirect effect.

Metabolic syndrome, wherein patients have both diabetes mellitus and dyslipidemia, is reaching epidemic proportions due to dietary factors and sedentary lifestyles.1) A major cause of mortality in these patients is atherosclerotic macrovascular diseases, the majority of which result from dyslipidemia associated with insulin-resistant diabetes. Adipose tissues, which were once thought to function primarily as passive depots for storage of excess lipid, are now understood to play crucial roles in metabolic regulation, feeding behavior and secretion of a variety of metabolic hormones. 2,3)Excessive accumulation of adipose cells in obesity contributes to the development of metabolic and cardiovascular diseases, as well as certain cancers. 4,5) Adipocytes accumulate energy in the form of triacylglycerols, which can be hydrolyzed and released as glycerol plus free fatty acids. When energy intake is dominant, excess lipid storage in white adipose tissues can be established through an increase in the size of mature adipocytes and/or recruitment of preadipocytes. This situation may lead not only to obesity but also to related pathophysiological conditions, such as type 2 diabetes mellitus, since adipose tissues are not only insulin-responsive tissues that convert glucose into fat stores, but also endocrine organs participating in energy balance regulation.6,7) Adipogenesis has been extensively studied in vitro using murine preadipocyte lineages and rat white adipocytes. Adipose conversion from such fibroblastic precursors is divided into at least three steps, namely cell commitment, clonal amplification and phenotype expression. 8)The initial step involves the induction of expression of several adipose-specific genes, whereas later events result in the appearance of the functional characteristics of mature adipocytes, such as increased glucose transport capacity, through the expression of insulin-responsive glucose transporters, which represent a key step in lipogenesis, thereby leading to progressive lipid accumulation. As a key factor for controlling the adipose mass in adipocytes, examination of the inhibitory activities of substances on excess lipid storage in white adipocytes represents a rational strategy for preventing obesity.Orengedokuto (OGT), Bofutsushosan (BTS) and Boiogito (BOT) are well-known Japanese, Korean and Chinese traditional herbal medicines used to clinically prevent or improve obesity. BTS has been reported to inhibit atherosclerosis, 9) obesity, 10) hypertension 11) and hyperglycemia. 12) However, Three Kampo medicines, Boiogito (BOT), Bofutsushosan (BTS) and Orengedokuto (OGT), used for obese patients were investigated for their effects on adipogenesis in cultured rat white adipocytes. Administration of the three extracts suppressed adipogenesis in concentration-dependent manners (1-100 m mg/ml) without any cytotoxicity. Changes in mRNA expression levels were analyzed using a Rat 230 2.0 Affymetrix GeneChip® microarray system. DNA microarray analysis (total probe set: 31099) using cDNAs prepared...