Laboratorio de Biología Molecular de Trypanosoma cruzi (LBMTC), Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina.
PLoS Negl Trop Dis. 2013;7(2):e2044. doi: 10.1371/journal.pntd.0002044. Epub 2013 Feb 7.
Trypanosoma cruzi, the etiological agent of Chagas' disease, is an early divergent eukaryote in which control of gene expression relies mainly in post-transcriptional mechanisms. Transcription levels are globally up and down regulated during the transition between proliferating and non-proliferating life-cycle stages. In this work we characterized a nuclear adenylate kinase isoform (TcADKn) that is involved in ribosome biogenesis. Nuclear adenylate kinases have been recently described in a few organisms, being all related to RNA metabolism. Depending on active transcription and translation, TcADKn localizes in the nucleolus or the cytoplasm. A non-canonical nuclear localization signal was mapped towards the N-terminal of the protein, being the phosphate-binding loop essential for its localization. In addition, TcADKn nuclear exportation depends on the nuclear exportation adapter CRM1. TcADKn nuclear shuttling is governed by nutrient availability, oxidative stress and by the equivalent in T. cruzi of the mammalian TOR (Target of Rapamycin) pathway. One of the biological functions of TcADKn is ribosomal 18S RNA processing by direct interaction with ribosomal protein TcRps14. Finally, TcADKn expression is regulated by its 3' UTR mRNA. Depending on extracellular conditions, cells modulate protein translation rates regulating ribosome biogenesis and nuclear adenylate kinases are probably key components in these processes.
克氏锥虫，恰加斯病的病原体，是一种早期分化的真核生物，其基因表达的调控主要依赖于转录后机制。在增殖和非增殖生命周期阶段之间的转换过程中，转录水平全面上调和下调。在这项工作中，我们鉴定了一种参与核糖体生物发生的核腺苷酸激酶同工型（TcADKn）。核腺苷酸激酶最近在一些生物体中被描述，它们都与 RNA 代谢有关。根据转录和翻译的活性，TcADKn 定位在核仁或细胞质中。一个非典型的核定位信号被映射到蛋白的 N 端，磷酸结合环对于其定位是必需的。此外，TcADKn 的核输出依赖于核输出适配器 CRM1。TcADKn 的核穿梭受营养物质可用性、氧化应激以及 T. cruzi 中相当于哺乳动物 TOR（雷帕霉素靶蛋白）途径的调控。TcADKn 的生物学功能之一是通过与核糖体蛋白 TcRps14 的直接相互作用来处理核糖体 18S RNA。最后，TcADKn 的表达受其 3'UTR mRNA 的调控。根据细胞外条件的不同，细胞调节核糖体生物发生的蛋白质翻译速率，核腺苷酸激酶可能是这些过程的关键组成部分。
