Sperling Ruth
Department of Genetics, The Hebrew University of Jerusalem, Jerusalem, Israel.
Wiley Interdiscip Rev RNA. 2017 Jan;8(1). doi: 10.1002/wrna.1377. Epub 2016 Jul 27.
The complex life of pre-mRNA from transcription to the production of mRNA that can be exported from the nucleus to the cytoplasm to encode for proteins entails intricate coordination and regulation of a network of processing events. Coordination is required between transcription and splicing and between several processing events including 5' and 3' end processing, splicing, alternative splicing and editing that are major contributors to the diversity of the human proteome, and occur within a huge and dynamic macromolecular machine-the endogenous spliceosome. Detailed mechanistic insight of the splicing reaction was gained from studies of the in vitro spliceosome assembled on a single intron. Because most pre-mRNAs are multiintronic that undergo alternative splicing, the in vivo splicing machine requires additional elements to those of the in vitro machine, to account for all these diverse functions. Information about the endogenous spliceosome is emerging from imaging studies in intact and live cells that support the cotranscriptional commitment to splicing model and provide information about splicing kinetics in vivo. Another source comes from studies of the in vivo assembled spliceosome, isolated from cell nuclei under native conditions-the supraspliceosome-that individually package pre-mRNA transcripts of different sizes and number of introns into complexes of a unique structure, indicating their universal nature. Recent years have portrayed new players affecting alternative splicing and novel connections between splicing, transcription and chromatin. The challenge ahead is to elucidate the structure and function of the endogenous spliceosome and decipher the regulation and coordination of its network of processing activities. WIREs RNA 2017, 8:e1377. doi: 10.1002/wrna.1377 For further resources related to this article, please visit the WIREs website.
前体mRNA从转录到生成可从细胞核输出至细胞质以编码蛋白质的mRNA的复杂过程，需要对一系列加工事件网络进行精细的协调与调控。转录与剪接之间，以及包括5'和3'末端加工、剪接、可变剪接和编辑在内的多个加工事件之间都需要协调，这些加工事件是人类蛋白质组多样性的主要贡献因素，且发生在一个巨大且动态的大分子机器——内源性剪接体中。通过对在单个内含子上组装的体外剪接体的研究，人们获得了对剪接反应详细的机制性认识。由于大多数前体mRNA是多内含子的且会经历可变剪接，因此体内剪接机器需要体外剪接体之外的其他元件，以实现所有这些不同的功能。关于内源性剪接体的信息正从对完整活细胞的成像研究中浮现，这些研究支持转录共发生剪接模型，并提供体内剪接动力学的信息。另一个来源是对在体内组装的剪接体的研究，即在天然条件下从细胞核中分离出的超级剪接体，它将不同大小和内含子数量的前体mRNA转录本分别包装成具有独特结构的复合物，这表明了它们的普遍性质。近年来已发现了影响可变剪接的新因子，以及剪接、转录和染色质之间的新联系。未来的挑战是阐明内源性剪接体的结构与功能，并解读其加工活动网络的调控与协调机制。WIREs RNA 2017, 8:e1377. doi: 10.1002/wrna.1377 有关本文的更多资源，请访问WIREs网站。
