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DOI	10.1126/science.abc3753
	Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation
	Townsend C.; Leelaram M.N.; Agafonov D.E.; Dybkov O.; Will C.L.; Bertram K.; Urlaub H.; Kastner B.; Stark H.; Lührmann R.
发表日期	2020
ISSN	0036-8075
卷号	370 期号:6523
英文摘要	Spliceosome activation involves extensive protein and RNA rearrangements that lead to formation of a catalytically active U2/U6 RNA structure. At present, little is known about the assembly pathway of the latter and the mechanism whereby proteins aid its proper folding. Here, we report the cryo-electron microscopy structures of two human, activated spliceosome precursors (that is, pre-Bact complexes) at core resolutions of 3.9 and 4.2 angstroms. These structures elucidate the order of the numerous protein exchanges that occur during activation, the mutually exclusive interactions that ensure the correct order of ribonucleoprotein rearrangements needed to form the U2/U6 catalytic RNA, and the stepwise folding pathway of the latter. Structural comparisons with mature Bact complexes reveal the molecular mechanism whereby a conformational change in the scaffold protein PRP8 facilitates final three-dimensional folding of the U2/U6 catalytic RNA. © 2020 American Association for the Advancement of Science. All rights reserved.
英文关键词	small nuclear RNA; PRPF8 protein, human; ribozyme; RNA binding protein; small nuclear RNA; U2 small nuclear RNA; U6 small nuclear RNA; catalysis; experimental study; gene expression; physiological response; protein; RNA; Article; catalysis; complex formation; conformational transition; cryoelectron microscopy; human; priority journal; protein folding; protein protein interaction; protein RNA binding; RNA structure; spliceosome; chemistry; enzyme active site; genetics; protein conformation; RNA folding; RNA splicing; spliceosome; Catalytic Domain; Cryoelectron Microscopy; Humans; Protein Conformation; RNA Folding; RNA Splicing; RNA, Catalytic; RNA, Small Nuclear; RNA-Binding Proteins; Spliceosomes
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/245772
作者单位	Department of Structural Dynamics, Mpi for Biophysical Chemistry, Am Fassberg 11, Göttingen, D-37077, Germany; Cellular Biochemistry, Mpi for Biophysical Chemistry, Am Fassberg 11, Göttingen, D-37077, Germany; Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Am Fassberg 11, Göttingen, D-37077, Germany; Institute for Clinical Chemistry, University Medical Center Göttingen, Bioanalytics Group, Robert-Koch-Straße 40, Göttingen, D-37075, Germany
推荐引用方式 GB/T 7714	Townsend C.,Leelaram M.N.,Agafonov D.E.,et al. Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation[J],2020,370(6523).
APA	Townsend C..,Leelaram M.N..,Agafonov D.E..,Dybkov O..,Will C.L..,...&Lührmann R..(2020).Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation.Science,370(6523).
MLA	Townsend C.,et al."Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation".Science 370.6523(2020).