在剪接体的结构时代，遗传学和生物化学仍然至关重要。
Genetics and biochemistry remain essential in the structural era of the spliceosome.
作者信息
Mayerle Megan, Guthrie Christine
机构信息
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.
出版信息
Methods. 2017 Aug 1;125:3-9. doi: 10.1016/j.ymeth.2017.01.006. Epub 2017 Jan 26.
Abstract
The spliceosome is not a single macromolecular machine. Rather it is a collection of dynamic heterogeneous subcomplexes that rapidly interconvert throughout the course of a typical splicing cycle. Because of this, for many years the only high resolution structures of the spliceosome available were of smaller, isolated protein or RNA components. Consequently much of our current understanding of the spliceosome derives from biochemical and genetic techniques. Now with the publication of multiple, high resolution structures of the spliceosome, some question the relevance of traditional biochemical and genetic techniques to the splicing field. We argue such techniques are not only relevant, but vital for an in depth mechanistic understanding of pre-mRNA splicing.
摘要
剪接体不是一个单一的大分子机器。相反，它是一组动态的异质亚复合物，在典型的剪接循环过程中会迅速相互转换。正因如此，多年来可用的剪接体的唯一高分辨率结构是较小的、分离的蛋白质或RNA组分的结构。因此，我们目前对剪接体的许多理解都来自生化和遗传学技术。现在，随着多个剪接体高分辨率结构的发表，一些人质疑传统生化和遗传学技术在剪接领域的相关性。我们认为这些技术不仅相关，而且对于深入理解前体mRNA剪接的机制至关重要。
相似文献
1
Genetics and biochemistry remain essential in the structural era of the spliceosome.在剪接体的结构时代，遗传学和生物化学仍然至关重要。
Methods. 2017 Aug 1;125:3-9. doi: 10.1016/j.ymeth.2017.01.006. Epub 2017 Jan 26.
2
Mechanistic insights into precursor messenger RNA splicing by the spliceosome.剪接体对前体信使 RNA 剪接的机制见解。
Nat Rev Mol Cell Biol. 2017 Nov;18(11):655-670. doi: 10.1038/nrm.2017.86. Epub 2017 Sep 27.
3
Quantifying the ratio of spliceosome components assembled on pre-mRNA.定量组装在信使核糖核酸前体上的剪接体成分的比例。
Methods Mol Biol. 2014;1126:257-69. doi: 10.1007/978-1-62703-980-2_19.
4
Using yeast genetics to study splicing mechanisms.利用酵母遗传学研究剪接机制。
Methods Mol Biol. 2014;1126:285-98. doi: 10.1007/978-1-62703-980-2_21.
5
Mechanisms of spliceosomal assembly.剪接体组装机制。
Methods Mol Biol. 2014;1126:35-43. doi: 10.1007/978-1-62703-980-2_3.
6
The pre-mRNA splicing reaction.前体信使核糖核酸剪接反应。
Methods Mol Biol. 2014;1126:3-12. doi: 10.1007/978-1-62703-980-2_1.
7
Structural studies of the spliceosome: past, present and future perspectives.剪接体的结构研究：过去、现在和未来的展望。
Biochem Soc Trans. 2018 Dec 17;46(6):1407-1422. doi: 10.1042/BST20170240. Epub 2018 Nov 12.
8
Group II intron lariat: Structural insights into the spliceosome.II组内含子套索：剪接体的结构见解
RNA Biol. 2015;12(9):913-7. doi: 10.1080/15476286.2015.1066956.
9
Structural studies of the endogenous spliceosome - The supraspliceosome.内源性剪接体的结构研究——超级剪接体
Methods. 2017 Aug 1;125:70-83. doi: 10.1016/j.ymeth.2017.04.005. Epub 2017 Apr 13.
10
The spliceosome and its metal ions.剪接体及其金属离子。
Met Ions Life Sci. 2011;9:235-51. doi: 10.1039/9781849732512-00235.
引用本文的文献
1
A forward genetic screen in C. elegans identifies conserved residues of spliceosomal proteins PRP8 and SNRNP200/BRR2 with a role in maintaining 5' splice site identity.秀丽隐杆线虫中的正向遗传学筛选鉴定出剪接体蛋白 PRP8 和 SNRNP200/BRR2 的保守残基在维持 5' 剪接位点同一性方面起作用。
Nucleic Acids Res. 2022 Nov 11;50(20):11834-11857. doi: 10.1093/nar/gkac991.
2
Transcript-specific determinants of pre-mRNA splicing revealed through in vivo kinetic analyses of the 1 and 2 chemical steps.通过对 1 和 2 化学步骤的体内动力学分析揭示了前体 mRNA 剪接的转录本特异性决定因素。
Mol Cell. 2022 Aug 18;82(16):2967-2981.e6. doi: 10.1016/j.molcel.2022.06.020. Epub 2022 Jul 12.
3
A genetic screen in C. elegans reveals roles for KIN17 and PRCC in maintaining 5' splice site identity.在秀丽隐杆线虫中的遗传筛选揭示了 KIN17 和 PRCC 在维持 5' 剪接位点同一性中的作用。
PLoS Genet. 2022 Feb 10;18(2):e1010028. doi: 10.1371/journal.pgen.1010028. eCollection 2022 Feb.
4
Structural basis for conformational equilibrium of the catalytic spliceosome.催化剪接体构象平衡的结构基础。
Mol Cell. 2021 Apr 1;81(7):1439-1452.e9. doi: 10.1016/j.molcel.2021.02.021. Epub 2021 Mar 10.
5
Saccharomyces cerevisiae Ecm2 Modulates the Catalytic Steps of pre-mRNA Splicing.酿酒酵母Ecm2调节前体mRNA剪接的催化步骤。
RNA. 2021 Feb 5;27(5):591-603. doi: 10.1261/rna.077727.120.
6
Blocking late stages of splicing quickly limits pre-spliceosome assembly in vivo.阻断剪接晚期过程可快速限制剪接前体在体内的组装。
RNA Biol. 2019 Dec;16(12):1775-1784. doi: 10.1080/15476286.2019.1657788. Epub 2019 Sep 4.
7
Global donor and acceptor splicing site kinetics in human cells.人类细胞中的全球供体和受体剪接位点动力学。
Elife. 2019 Apr 26;8:e45056. doi: 10.7554/eLife.45056.
8
An Allosteric Network for Spliceosome Activation Revealed by High-Throughput Suppressor Analysis in .高通量抑制分析揭示剪接体激活的别构网络。
Genetics. 2019 May;212(1):111-124. doi: 10.1534/genetics.119.301922. Epub 2019 Mar 21.
9
SNRP-27, the homolog of the tri-snRNP 27K protein, has a role in 5' splice site positioning in the spliceosome.SNRP-27 是三 snRNP 27K 蛋白的同源物，在剪接体中 5' 剪接位点定位中发挥作用。
RNA. 2018 Oct;24(10):1314-1325. doi: 10.1261/rna.066878.118. Epub 2018 Jul 13.
10
Structural dynamics of the N-terminal domain and the Switch loop of Prp8 during spliceosome assembly and activation.剪接体组装和激活过程中 Prp8 N 端结构域和 Switch 环的结构动力学。
Nucleic Acids Res. 2018 May 4;46(8):3833-3840. doi: 10.1093/nar/gky242.
本文引用的文献
1
Cryo-EM structure of a human spliceosome activated for step 2 of splicing.冷冻电镜结构解析人类剪接体在剪接步骤 2 的激活状态。
Nature. 2017 Feb 16;542(7641):318-323. doi: 10.1038/nature21079. Epub 2017 Jan 11.
2
Structure of a spliceosome remodelled for exon ligation.为外显子连接而重塑的剪接体结构。
Nature. 2017 Feb 16;542(7641):377-380. doi: 10.1038/nature21078. Epub 2017 Jan 11.
3
Molecular architecture of the Saccharomyces cerevisiae activated spliceosome.酿酒酵母激活剪接体的分子结构。
Science. 2016 Sep 23;353(6306):1399-1405. doi: 10.1126/science.aag1906. Epub 2016 Aug 25.
4
Cryo-EM structure of the spliceosome immediately after branching.分支后剪接体的冷冻电镜结构
Nature. 2016 Sep 8;537(7619):197-201. doi: 10.1038/nature19316. Epub 2016 Jul 26.
5
Structure of a yeast catalytic step I spliceosome at 3.4 Å resolution.酵母催化步骤 I 剪接体的结构在 3.4 Å 分辨率下。
Science. 2016 Aug 26;353(6302):895-904. doi: 10.1126/science.aag2235. Epub 2016 Jul 21.
6
Structure of a yeast activated spliceosome at 3.5 Å resolution.酵母激活剪接体的 3.5Å 分辨率结构。
Science. 2016 Aug 26;353(6302):904-11. doi: 10.1126/science.aag0291. Epub 2016 Jul 21.
7
Splicing Factor Mutations in Cancer.癌症中的剪接因子突变
Adv Exp Med Biol. 2016;907:215-28. doi: 10.1007/978-3-319-29073-7_9.
8
Single molecule analysis reveals reversible and irreversible steps during spliceosome activation.单分子分析揭示了剪接体激活过程中的可逆和不可逆步骤。
Elife. 2016 May 31;5:e14166. doi: 10.7554/eLife.14166.
9
Crystal structures of a group II intron maturase reveal a missing link in spliceosome evolution.II 组内含子成熟酶的晶体结构揭示了剪接体进化中缺失的环节。
Nat Struct Mol Biol. 2016 Jun;23(6):558-65. doi: 10.1038/nsmb.3224. Epub 2016 May 2.
10
Spliceosomal DEAH-Box ATPases Remodel Pre-mRNA to Activate Alternative Splice Sites.剪接体DEAH盒ATP酶重塑前体mRNA以激活可变剪接位点。
Cell. 2016 Feb 25;164(5):985-98. doi: 10.1016/j.cell.2016.01.025.
Zotero 插件