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Intricacies in the cross talk between metabolic enzymes, RNA, and protein translation.
Journal of Molecular Cell Biology ( IF 5.5 ) Pub Date : 2019-09-03 , DOI: 10.1093/jmcb/mjz089
Yuan Lv 1, 2, 3, 4, 5 , Muqddas Tariq 1, 2, 3, 4, 5 , Xiangpeng Guo 1, 2, 3, 4 , Shahzina Kanwal 1, 2, 3, 4 , Miguel A Esteban 1, 2, 3, 4, 6
Affiliation  

The development of techniques allowing the systematic capture of the RNA-bound proteome has yielded many surprises. Among these, metabolic enzymes have been frequently detected as RNA-binding proteins (RBPs) by different profiling methodologies in various cell types (Hentze et al., 2018). Compared to previous—more simplistic—views, it is now known that cellular metabolism (not only limited to the tricarboxylic acid, TCA, cycle) is compartmentalized. In fact, metabolic enzymes translocate to the nucleus and are enriched at actively transcribed loci, where they sustain epigenetic/epitranscriptomic marks through localized metabolite production (Mews et al., 2017). It has been proposed that the interaction with nascent RNAs facilitates the anchorage of metabolic enzymes at target loci (Bao et al., 2018), and it is plausible that mature RNAs work in the same way to assist metabolic reactions in the cytoplasm. Yet, it is becoming increasingly evident that the interaction of metabolic enzymes with RNA also has metabolism-independent functions, and protein translation is emerging as a key missing nexus (Figure 1A). For example, the glycolytic enzyme pyruvate kinase muscle 2 (PKM2) promotes protein translation through simultaneous binding to target mRNAs and ribosomal components (Simsek et al., 2017). Thus, deeper understanding of the relationship between RNA and metabolic enzymes is necessary for gaining a complete model of metabolism and other cellular functions as a whole.

中文翻译:

代谢酶,RNA和蛋白质翻译之间相互影响的复杂性。

允许系统捕获RNA结合的蛋白质组的技术的发展带来了许多惊喜。其中,在各种细胞类型中,通过不同的分析方法,代谢酶经常被检测为RNA结合蛋白(RBP)(Hentze et al。,2018)。与以前(更简单)的观点相比,现在知道细胞代谢(不仅限于三羧酸,TCA循环)是分隔的。实际上,代谢酶易位至细胞核并在活跃转录的基因座富集,在这些酶中它们通过局部代谢产物的产生维持表观遗传/上皮转录组标记(Mews等,2017)。有人提出,与新生RNA的相互作用可促进代谢酶在靶基因位点的锚定(Bao等人,2018),成熟的RNA可以以相同的方式协助细胞质中的代谢反应,这似乎是合理的。然而,越来越明显的是,代谢酶与RNA的相互作用也具有与代谢无关的功能,并且蛋白质翻译正逐渐成为关键的缺失纽带(图1A)。例如,糖酵解酶丙酮酸激酶肌肉2(PKM2)通过同时与靶标mRNA和核糖体成分结合来促进蛋白质翻译(Simsek等,2017)。因此,对RNA和代谢酶之间关系的更深入了解对于获得完整的代谢和其他细胞功能的完整模型是必要的。越来越明显的是,代谢酶与RNA的相互作用也具有不依赖于代谢的功能,并且蛋白质翻译正逐渐成为关键的缺失纽带(图1A)。例如,糖酵解酶丙酮酸激酶肌肉2(PKM2)通过同时与靶标mRNA和核糖体成分结合来促进蛋白质翻译(Simsek等,2017)。因此,对RNA和代谢酶之间关系的更深入了解对于获得完整的代谢和其他细胞功能的完整模型是必要的。越来越明显的是,代谢酶与RNA的相互作用也具有不依赖于代谢的功能,并且蛋白质翻译正逐渐成为关键的缺失纽带(图1A)。例如,糖酵解酶丙酮酸激酶肌肉2(PKM2)通过同时与靶标mRNA和核糖体成分结合来促进蛋白质翻译(Simsek等,2017)。因此,对RNA和代谢酶之间关系的更深入了解对于获得完整的代谢和其他细胞功能的完整模型是必要的。
更新日期:2019-09-03
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