The spliceosomal PRP19 complex of trypanosomes

In trypanosomes, mRNAs are processed by spliced leader (SL) trans splicing, in which a capped SL, derived from SL RNA, is spliced onto the 5′ end of each mRNA. This process is mediated by the spliceosome, a large and dynamic RNA‐protein machinery consisting of small nuclear ribonucleoproteins (snRNPs) and non‐snRNP proteins. Due to early evolutionary divergence, the amino acid sequences of trypanosome splicing factors exhibit limited similarity to those of their eukaryotic orthologs making their bioinformatic identification challenging. Most of the ～ 60 protein components that have been characterized thus far are snRNP proteins because, in contrast to individual snRNPs, purification of intact spliceosomes has not been achieved yet. Here, we characterize the non‐snRNP PRP19 complex of Trypanosoma brucei. We identified a complex that contained the core subunits PRP19, CDC5, PRL1, and SPF27, as well as PRP17, SKIP and PPIL1. Three of these proteins were newly annotated. The PRP19 complex was associated primarily with the activated spliceosome and, accordingly, SPF27 silencing blocked the first splicing step. Interestingly, SPF27 silencing caused an accumulation of SL RNA with a hypomethylated cap that closely resembled the defect observed previously upon depletion of the cyclin‐dependent kinase CRK9, indicating that both proteins may function in spliceosome activation.     

未折叠蛋白反应—细胞内信号传导新途径

真核细胞中,当未折叠的蛋白在内质网上增多的时候,一系列内质网居民蛋白基因的转录也随之增加,这称为未折叠蛋白反应（unfolded protein response,UPR)。在酵母细胞中未折叠蛋白的感受器是Irelp蛋白,它能检测到未折叠蛋白的聚集,并将信号传递到细胞核内,诱导UPR特异转录因子Haclp mRNA的剪接成熟。成熟的Haclp蛋白能通过与UPR元件（UPR－element)的结合诱导含有这一元件的基因转录,从而启动UPR。在UPR信号传递途径中,磷酸化的Irelp与Gcn5/Ada复合物可通过解开染色体促进Haclp活性的发挥,而Ptc2p能通过使Irelp去磷酸化而反向调节UPR。目前发现UPR与磷脂生物合成存在交叉的共同途径,人类中也存在Irelp的类似物。