CHERP Regulates the Alternative Splicing of pre-mRNAs in the Nucleus.

Calcium homeostasis endoplasmic reticulum protein (CHERP) is colocalized with the inositol 1,4,5-trisphosphate receptor (IP3R) in the endoplasmic reticulum or perinuclear region, and has been involved in intracellular calcium signaling. Structurally, CHERP carries the nuclear localization signal and arginine/serine-dipeptide repeats, like domain, and interacts with the spliceosome. However, the exact function of CHERP in the nucleus remains unknown. Here, we showed that poly(A)+ RNAs accumulated in the nucleus of CHERP-depleted U2OS cells. Our global analysis revealed that CHERP regulated alternative mRNA splicing events by interaction with U2 small nuclear ribonucleoproteins (U2 snRNPs) and U2 snRNP-related proteins. Among the five alternative splicing patterns analyzed, intron retention was the most frequently observed event. This was in accordance with the accumulation of poly(A)+ RNAs in the nucleus. Furthermore, intron retention and cassette exon choices were influenced by the strength of the 5' or 3' splice site, the branch point site, GC content, and intron length. In addition, CHERP depletion induced anomalies in the cell cycle progression into the M phase, and abnormal cell division. These results suggested that CHERP is involved in the regulation of alternative splicing.

Cost analysis of four types of surgeries for pelvic organ prolapse in a Japanese population.

INTRODUCTION AND HYPOTHESIS: To compare the perioperative costs analysis between laparoscopic/transvaginal and the mesh/non-mesh surgeries for pelvic organ prolapse (POP) in Japan. MATERIALS AND METHODS: From April 2013 to April 2017, 890 patients who underwent POP surgeries were enrolled in this study. Regarding transvaginal native tissue repair (TV-NTR: transvaginal hysterectomy with colpocleisis), transvaginal mesh surgery (TVM), laparoscopic native tissue repair (L-NTR: laparoscopic hysterectomy and uterosacral ligament colposuspension), and laparoscopic sacrocolpopexy (LSC), a retrospective observational study was performed. Patients' age, operation time, blood loss, perioperative complications, length of hospital stay, pre-/postoperative quality of life (QOL) scores, were reviewed from the medical records. The net income, which was calculated by using the income (the operation/anesthesia fee) and the costs (the labor and consumables costs for operation/anesthesia), was evaluated. RESULTS: The operation fees of the L-NTR ($4250) and the LSC ($4833) groups were higher than that of the TV-NTR ($2652) and the TVM ($2913) groups. The labor costs and consumables costs of operation were higher in the LSC ($1589) and the L-NTR ($1500) groups than the TV-NTR ($180) and the TVM ($178) groups. The consumables costs for anesthesia in the four groups were equal. The operation hours were significantly shorter in the TV-NTR and the TVM groups than the L-NTR and the LSC groups. CONCLUSIONS: We found that TVM operation was an economically excellent and the most efficient POP operation with shorter operation time and less consumables.

Regulating Divergent Transcriptomes through mRNA Splicing and Its Modulation Using Various Small Compounds.

Human transcriptomes are more divergent than genes and contribute to the sophistication of life. This divergence is derived from various isoforms arising from alternative splicing. In addition, alternative splicing regulated by spliceosomal factors and RNA structures, such as the RNA G-quadruplex, is important not only for isoform diversity but also for regulating gene expression. Therefore, abnormal splicing leads to serious diseases such as cancer and neurodegenerative disorders. In the first part of this review, we describe the regulation of divergent transcriptomes using alternative mRNA splicing. In the second part, we present the relationship between the disruption of splicing and diseases. Recently, various compounds with splicing inhibitor activity were established. These splicing inhibitors are recognized as a biological tool to investigate the molecular mechanism of splicing and as a potential therapeutic agent for cancer treatment. Food-derived compounds with similar functions were found and are expected to exhibit anticancer effects. In the final part, we describe the compounds that modulate the messenger RNA (mRNA) splicing process and their availability for basic research and future clinical potential.