Identification of processing elements and interactors implicate SMN, coilin and the pseudogene-encoded coilp1 in telomerase and box C/D scaRNP biogenesis

Many cellular functions, such as translation, require ribonucleoproteins (RNPs). The biogenesis of RNPs is a multi-step process that, depending on the RNP, can take place in many cellular compartments. Here we examine 2 different RNPs: telomerase and small Cajal body-specific RNPs (scaRNPs). Both of these RNPs are enriched in the Cajal body (CB), which is a subnuclear domain that also has high concentrations of another RNP, small nuclear RNPs (snRNPs). SnRNPs are essential components of the spliceosome, and scaRNPs modify the snRNA component of the snRNP. The CB contains many proteins, including WRAP53, SMN and coilin, the CB marker protein. We show here that coilin, SMN and coilp1, a newly identified protein encoded by a pseudogene in human, associate with telomerase RNA and a subset of scaRNAs. We also have identified a processing element within box C/D scaRNA. Our findings thus further strengthen the connection between the CB proteins coilin and SMN in the biogenesis of telomeras e and box C/D scaRNPs, and reveal a new player, coilp1, that likely participates in this process.

诸多细胞生命活动（如翻译过程）均依赖核糖核蛋白（ribonucleoproteins, RNPs）。核糖核蛋白的生物发生是一个多步骤过程，其具体发生位点因核糖核蛋白类型而异，可遍布多个细胞区室。本研究聚焦两种不同的核糖核蛋白：端粒酶（telomerase）与小卡哈尔体特异性核糖核蛋白（small Cajal body-specific RNPs, scaRNPs）。这两类核糖核蛋白均富集于卡哈尔体（Cajal body, CB）——这是一种亚核结构域，同时也高浓度富集另一类核糖核蛋白：核小核糖核蛋白（small nuclear RNPs, snRNPs）。核小核糖核蛋白是剪接体的核心必需组分，而小卡哈尔体特异性核糖核蛋白可对核小核糖核蛋白的snRNA组分进行修饰。卡哈尔体含有多种蛋白，包括WRAP53、SMN以及作为该结构域标志物的科林蛋白（coilin）。本研究证实，科林蛋白、SMN以及由人类假基因编码的新发现蛋白coilp1，均可与端粒酶RNA及部分小卡哈尔体特异性RNA结合。本研究同时在box C/D型小卡哈尔体特异性RNA中鉴定出一处加工元件。综上，本研究进一步强化了卡哈尔体蛋白科林蛋白与SMN在端粒酶及box C/D型小卡哈尔体特异性核糖核蛋白生物发生过程中的关联，并揭示了可能参与该过程的新成员coilp1。