Fazal Furqan M, Chang Howard Y
Center for Personal Dynamic Regulomes, Stanford University, Stanford, California 94305, USA.
Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA.
Cold Spring Harb Symp Quant Biol. 2019;84:31-45. doi: 10.1101/sqb.2019.84.040352. Epub 2020 Jun 1.
RNAs are trafficked and localized with exquisite precision inside the cell. Studies of candidate messenger RNAs have shown the vital importance of RNA subcellular location in development and cellular function. New sequencing- and imaging-based methods are providing complementary insights into subcellular localization of RNAs transcriptome-wide. APEX-seq and ribosome profiling as well as proximity-labeling approaches have revealed thousands of transcript isoforms are localized to distinct cytotopic locations, including locations that defy biochemical fractionation and hence were missed by prior studies. Sequences in the 3' and 5' untranslated regions (UTRs) serve as "zip codes" to direct transcripts to particular locales, and it is clear that intronic and retrotransposable sequences within transcripts have been co-opted by cells to control localization. Molecular motors, nuclear-to-cytosol RNA export, liquid-liquid phase separation, RNA modifications, and RNA structure dynamically shape the subcellular transcriptome. Location-based RNA regulation continues to pose new mysteries for the field, yet promises to reveal insights into fundamental cell biology and disease mechanisms.
RNA在细胞内以极高的精度进行运输和定位。对候选信使RNA的研究表明，RNA亚细胞定位在发育和细胞功能中至关重要。基于测序和成像的新方法正在全转录组范围内为RNA的亚细胞定位提供互补的见解。APEX-seq、核糖体谱分析以及邻近标记方法已经揭示了数千种转录本异构体定位于不同的细胞位置，包括那些无法通过生化分级分离检测到的位置，因此之前的研究未能发现这些位置。3'和5'非翻译区（UTR）中的序列充当“邮政编码”，将转录本引导至特定位置，很明显，转录本中的内含子和逆转座子序列已被细胞利用来控制定位。分子马达、核到细胞质的RNA输出、液-液相分离、RNA修饰和RNA结构动态地塑造了亚细胞转录组。基于位置的RNA调控继续给该领域带来新的谜团，但有望揭示对基础细胞生物学和疾病机制的深入理解。
