Structural basis of human SNAPc recognizing proximal sequence element of snRNA promoter

Jianfeng Sun (), Xue Li, Xuben Hou, Sujian Cao, Wenjin Cao, Ye Zhang, Jinyang Song, Manfu Wang, Hao Wang, Xiaodong Yan, Zengpeng Li, Robert G. Roeder () and Wei Wang ()
Additional contact information
Jianfeng Sun: Shandong University
Xue Li: Shandong University
Xuben Hou: Shandong University
Sujian Cao: Shandong University
Wenjin Cao: Shandong University
Ye Zhang: Shandong University
Jinyang Song: Shandong University
Manfu Wang: Wuxi Biortus Biosciences Co. Ltd.
Hao Wang: Shandong University
Xiaodong Yan: Wuxi Biortus Biosciences Co. Ltd.
Zengpeng Li: Ministry of Natural Resources
Robert G. Roeder: The Rockefeller University
Wei Wang: Shandong University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract In eukaryotes, small nuclear RNAs (snRNAs) function in many fundamental cellular events such as precursor messenger RNA splicing, gene expression regulation, and ribosomal RNA processing. The snRNA activating protein complex (SNAPc) exclusively recognizes the proximal sequence element (PSE) at snRNA promoters and recruits RNA polymerase II or III to initiate transcription. In view that homozygous gene-knockout of SNAPc core subunits causes mouse embryonic lethality, functions of SNAPc are almost housekeeping. But so far, the structural insight into how SNAPc assembles and regulates snRNA transcription initiation remains unclear. Here we present the cryo-electron microscopy structure of the essential part of human SNAPc in complex with human U6-1 PSE at an overall resolution of 3.49 Å. This structure reveals the three-dimensional features of three conserved subunits (N-terminal domain of SNAP190, SNAP50, and SNAP43) and explains how they are assembled into a stable mini-SNAPc in PSE-binding state with a “wrap-around” mode. We identify three important motifs of SNAP50 that are involved in both major groove and minor groove recognition of PSE, in coordination with the Myb domain of SNAP190. Our findings further elaborate human PSE sequence conservation and compatibility for SNAPc recognition, providing a clear framework of snRNA transcription initiation, especially the U6 system.

Date: 2022
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DOI: 10.1038/s41467-022-34639-1

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