Molecular architecture of the human 17S U2 snRNP

doi:10.1038/s41586-020-2344-3

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2344-3
	Molecular architecture of the human 17S U2 snRNP
	Muench, David E.1,2,3; Olsson, Andre 1,2; Ferchen, Kyle 1,2,4; Pham, Giang 5; Serafin, Rachel A.1,2; Chutipongtanate, Somchai 4,6; Dwivedi, Pankaj 4; Song, Baobao 1,2,7; Hay, Stuart 8; Chetal, Kashish 8; Trump-Durbin, Lisa R.9; Mookerjee-Basu, Jayati 10; Zhang, Kejian 11,12; Yu, Jennifer C.13,14
	2020-04-22
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	583 期号:7815 页码:310-+
文章类型	Article
语种	英语
国家	Germany; USA
英文关键词	The U2 small nuclear ribonucleoprotein (snRNP) has an essential role in the selection of the precursor mRNA branch-site adenosine, the nucleophile for the first step of splicing' . Stable addition of U2 during early spliceosome formation requiresthe DEAD-box ATPase PRP5(2-7). Yeast U2 small nuclear RNA (snRNA) nucleotides that form base pairs with the branch site are initially sequestered in a branchpoint-interacting stem-loop (BSL)(8), but whether the human U2 snRNA folds in a similar manner is unknown. The U2 SF3B1 protein, a common mutational target in haematopoietic cancers(9), contains a HEAT domain (SF3B1(HEAT)) with an open conformation in isolated SF3b(10), but a closed conformation in spliceosomes(11), which is required for stable interaction between U2 and the branch site. Here we report a 3D cryo-electron microscopy structure ofthe human 17S U2 snRNP at a core resolution of 4.1 angstrom and combine it with protein crosslinking data to determine the molecular architecture of this snRNP. Our structure reveals that SF3B1(HEAT) interacts with PRP5 and TAT-SF1, and maintains its open conformation in U2 snRNP, and that U2 snRNA forms a BSL that is sandwiched between PRP5, TAT-SF1 and SF3B1(HEAT). Thus, substantial remodelling of the BSL and displacement of BSL-interacting proteins must occur to allow formation of the U2-branch-site helix. Our studies provide a structural explanation of why TAT-SF1 must be displaced before the stable addition of U2 to the spliceosome, and identify RNP rearrangements facilitated by PRP5 that are required for stable interaction between U2 and the branch site.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000546767100025
WOS关键词	SMALL NUCLEAR RIBONUCLEOPROTEIN ; CRYO-EM STRUCTURE ; INTERACTION NETWORK ; HUMAN SPLICEOSOME ; ATPASE PRP5 ; RNA ; PROTEINS ; RECOGNITION ; ASSOCIATION ; SELECTION
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281549
专题	地球科学资源环境科学气候变化
作者单位	1.Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA; 2.Cincinnati Childrens Hosp Med Ctr, Ctr Syst Immunol, Cincinnati, OH 45229 USA; 3.Cincinnati Childrens Hosp Med Ctr, Mol & Dev Biol Grad Program, Cincinnati, OH 45229 USA; 4.Univ Cincinnati, Dept Canc Biol, Cincinnati, OH USA; 5.Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA; 6.Mahidol Univ, Pediat Translat Res Unit, Dept Pediat, Fac Med,Ramathibodi Hosp, Bangkok, Thailand; 7.Cincinnati Childrens Hosp Med Ctr, Immunol Grad Program, Cincinnati, OH 45229 USA; 8.Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA; 9.Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA; 10.Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA; 11.Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA; 12.Univ Cincinnati, Dept Pediat, Cincinnati, OH USA; 13.Rady Childrens Hosp San Diego, Div Pediat Hematol Oncol, San Diego, CA USA; 14.Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA; 15.Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH 45229 USA; 16.BioLegend Inc, San Diego, CA USA
推荐引用方式 GB/T 7714	Muench, David E.,Olsson, Andre,Ferchen, Kyle,et al. Molecular architecture of the human 17S U2 snRNP[J]. NATURE,2020,583(7815):310-+.
APA	Muench, David E..,Olsson, Andre.,Ferchen, Kyle.,Pham, Giang.,Serafin, Rachel A..,...&Yu, Jennifer C..(2020).Molecular architecture of the human 17S U2 snRNP.NATURE,583(7815),310-+.
MLA	Muench, David E.,et al."Molecular architecture of the human 17S U2 snRNP".NATURE 583.7815(2020):310-+.