A molecular brake that modulates spliceosome pausing at detained introns contributes to neurodegeneration

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the Bact state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration.

Expression of the Snail,Slug,and E-cadherin and their clinical significance in nasopharyngeal carcinoma / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the expression of transcription factors Snail,Slug and cell adhesion molecule E-cadherin in nasopharyngeal carcinoma(NPC)and evaluate their relationship with clinical pathological features and metastases.METHODS Immunohistochemistry and quantitative polymerase chain reaction were carried out to detect the expression of Snail,Slug and E-cadherin in 65 NPC samples and normal nasopharyngeal mucosa(18 cases).The expression of Snail and Ecadherin in distinct differentiation nasopharyngeal carcinoma was analyzed and the relationship of them with clinical pathological features was discussed.RESULTS Real-time PCR analysis and immunohistochemistry showed that Slug was elevated with increasing tumor grade.E-cadherin expression was reduced corresponding with prognostic indices and tumor.Snail showed no obvious change.The relative expression levels of E-cadherin mRNA were significantly different between lymph node metastasis group and nometastasis group(P

CT measure of pharynx of OSAHS patients / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the location and degree of pharyngeal narrowing in patients with ob-structive sleep apnea-hypopnea syndrome(OSAHS). METHODS Fifty patients with OSAHS were divided into two groups. The first group was examined with single layer helix CT at an awaken state. The second group was examined with single and 16 layer helix CT at an asleep state. Control group was 225 healthy adults. RESULTS The average minimum diameter of pharynx at soft palate level was 5.85 mm and the aver-age minimum section proportion was 50.3 mm2 in the first group. The average minimum diameter and the av-erage minimum section proportion of pharynx at soft palate level were 2.88 mm and 31.5 mm2, and 1.62 mm and 6.3 mm2 as examined with single layer and 16 lay-ers helix CT scan respectively in the second group. CONCLUSION CT can be used as a method for esti-mating the degree of pharyngeal narrowing in patients with OSAHS. 16 layer helix CT scan can reflect the actual pharyngeal narrowing in OSAHS patients while sleeping more accurately.