Distant coupling between RNA editing and alternative splicing of the osmosensitive cation channel Tmem63b.

Post-transcriptional modifications of pre-mRNAs expand the diversity of proteomes in higher eukaryotes. In the brain, these modifications diversify the functional output of many critical neuronal signal molecules. In this study, we identified a brain-specific A-to-I RNA editing that changed glutamine to arginine (Q/R) at exon 20 and an alternative splicing of exon 4 in Tmem63b, which encodes a ubiquitously expressed osmosensitive cation channel. The channel isoforms lacking exon 4 occurred in ∼80% of Tmem63b mRNAs in the brain but were not detected in other tissues, suggesting a brain-specific splicing. We found that the Q/R editing was catalyzed by Adar2 (Adarb1) and required an editing site complementary sequence located in the proximal 5' end of intron 20. Moreover, the Q/R editing was almost exclusively identified in the splicing isoform lacking exon 4, indicating a coupling between the editing and the splicing. Elimination of the Q/R editing in brain-specific Adar2 knockout mice did not affect the splicing efficiency of exon 4. Furthermore, transfection with the splicing isoform containing exon 4 suppressed the Q/R editing in primary cultured cerebellar granule neurons. Thus, our study revealed a coupling between an RNA editing and a distant alternative splicing in the Tmem63b pre-mRNA, in which the splicing plays a dominant role. Finally, physiological analysis showed that the splicing and the editing coordinately regulate Ca2+ permeability and osmosensitivity of channel proteins, which may contribute to their functions in the brain.

[Safflower's origin and changes of producing areas].

Human's application of safflower (Carthamus tinctorius) has a long history, but the origin remains unclear. Safflower was introduced into China for traditional Chinese medicine, and Sichuan was major producing area. However, in recent years, the main producing area is in Xinjiang province, in contrast Sichuan safflower is difficult to find. By reading relevant document literature and the production and marketing information of safflower, and having field investigation in the main producing areas, the origin of safflower and the reasons of producing areas' changes were explored. The origin of safflower is considered as the Fertile Crescent in reasonably. The change of producing areas in China is effected by the factors of natural environment and society. The suitability of producing areas and quality of safflower still need to study further.

A new triterpenoid from Panax ginseng exhibits cytotoxicity through p53 and the caspase signaling pathway in the HepG2 cell line.

A new triterpenoid, 20(R),22(xi),24(S)-dammar-25(26)-ene-3beta,6 alpha,12 beta,20,22,24-hexanol (1), and three known triterpenoids, beta-D-glucopyranoside,(3beta,12 beta)-12,20-dihydroxydammar-24-en-3-yl,6-acetate (2), 20(R)-ginsenoside Rg3 (3), and 20(R)-ginsenoside Rh2 (4), were isolated from the leaves of Panax ginseng. Their structures were determined by chemical analysis and spectral methods (IR, 1D and 2D NMR, HR-ESI-MS). Compounds 1-4 were exhibited various degrees of cytotoxicity in the human hepatoma cell line, HepG2. Compound 1 had the highest cytotoxic potency, with an IC50 value of 20.1 microM, by stimulating p53-mediated cell cycle arrest at the G1 to S phase transition, leading to apoptosis via activation of the caspase signaling pathway.