Genome-wide analyses of metazoan messenger RNA （mRNA） species are unveiling the extensive transcriptional diversity generated by alternative splicing （AS）. Research is also beginning to identify the splicing facto...Genome-wide analyses of metazoan messenger RNA （mRNA） species are unveiling the extensive transcriptional diversity generated by alternative splicing （AS）. Research is also beginning to identify the splicing factors and AS events required to maintain the balance between stem cell renewal （i.e stemness properties） and differentiation. One set of proteins at the center of spliceosome biogenesis are the survival motor neuron （SMN） complex constituents, which have a critical role in the assembly of spliceosomal small nuclear ribonucleoproteins （snRNPs） in all cells. In this review we discuss what is currently known about how AS controls pluripotency and cell fate and consider how an increased requirement for splicing factors, including SMN, helps to maintain an enrichment of stem cell-specific AS events. Furthermore, we highlight studies showing that mutations in specific splicing factors can lead to the aberrant development, and cause targeted degeneration of the nervous system. Using SMN as an example, we discuss the perspective of how stem cell-specific changes in splicing factors can lead to developmental defects and the selective degeneration of particular tissues. Finally we consider the expanding role of SMN, and other splicing factors, in the regulation of gene expression in stem cell biology, thereby providing insight into a number of debilitating diseases.展开更多
文摘Genome-wide analyses of metazoan messenger RNA （mRNA） species are unveiling the extensive transcriptional diversity generated by alternative splicing （AS）. Research is also beginning to identify the splicing factors and AS events required to maintain the balance between stem cell renewal （i.e stemness properties） and differentiation. One set of proteins at the center of spliceosome biogenesis are the survival motor neuron （SMN） complex constituents, which have a critical role in the assembly of spliceosomal small nuclear ribonucleoproteins （snRNPs） in all cells. In this review we discuss what is currently known about how AS controls pluripotency and cell fate and consider how an increased requirement for splicing factors, including SMN, helps to maintain an enrichment of stem cell-specific AS events. Furthermore, we highlight studies showing that mutations in specific splicing factors can lead to the aberrant development, and cause targeted degeneration of the nervous system. Using SMN as an example, we discuss the perspective of how stem cell-specific changes in splicing factors can lead to developmental defects and the selective degeneration of particular tissues. Finally we consider the expanding role of SMN, and other splicing factors, in the regulation of gene expression in stem cell biology, thereby providing insight into a number of debilitating diseases.
文摘目的对贵阳地区孕妇人群脊髓性肌萎缩症(spinal muscular atrophy,SMA)携带者的筛查现状进行研究,并对高风险孕妇行产前基因诊断,防止SMA患儿的出生。方法应用多重荧光定量PCR技术,对贵州省人民医院2018年1月-2019年12月1163例常规产检孕妇的运动神经元存活基因1(survival motor neuron,SMN1)进行定量检测,筛查出SMA携带者,并计算携带者的频率。对携带者的配偶进行筛查,并为双方均为携带者的夫妇提供产前诊断。结果对13478例孕妇进行SMA携带者筛查宣教,有1163例孕妇自愿接受筛查,接受率为8.62%。在接受筛查的孕妇中,检出SMA携带者26例,携带率为1/45(检出率2.24%)。经遗传咨询,12例携带者的配偶自愿接受SMA筛查,接受率为46.15%。检测出同为SMA携带者的夫妇2对。对高风险胎儿进行产前基因诊断,检出SMA患者1例,携带者1例。结论对贵阳地区孕妇人群进行第一次大规模SMA携带者筛查,根据筛查情况制定基因检测策略。其筛查流程和经验或将有助于SMA遗传咨询和产前基因诊断在贵阳地区的推广,对于优生优育、有效预防SMA胎儿的出生具有重要的临床意义。
