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Title: The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3’-end processing

Abstract

Unlike canonical pre-mRNAs, animal replication-dependent histone pre-mRNAs lack introns and are processed at the 3’-end by a mechanism distinct from cleavage and polyadenylation. They have a 3’ stem loop and histone downstream element (HDE) that are recognized by stem-loop binding protein (SLBP) and U7 snRNP, respectively. The N-terminal domain (NTD) of Lsm11, a component of U7 snRNP, interacts with FLASH NTD and these two proteins recruit the histone cleavage complex containing the CPSF-73 endonuclease for the cleavage reaction. Here, we determined crystal structures of FLASH NTD and found that it forms a coiled-coil dimer. Using solution light scattering, we characterized the stoichiometry of the FLASH NTD-Lsm11 NTD complex and found that it is a 2:1 heterotrimer, which is supported by observations from analytical ultracentrifugation and crosslinking.

Authors:
 [1];  [2];  [1];  [3];  [3];  [3];  [2]; ORCiD logo [1]
  1. Columbia Univ., New York, NY (United States)
  2. National Yang-Ming Univ., Taipei (Taiwan)
  3. Univ. of North Carolina, Chapel Hill, NC (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
Sponsoring Org.:
National Institutes of Health (NIH); Taiwan Ministry of Science and Technology (MOST); • National Institute of General Medical Sciences (NIGMS); Howard Hughes Medical Institute (HHMI); USDOE Office of Science (SC)
OSTI Identifier:
1430295
Grant/Contract Number:  
[R35GM118093; S10OD012018; GM29832; 105-2320-B-010-012; 106-2320-B-010-013; S10 RR029205; AC02-06CH11357; AC02-05CH11231]
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
[ Journal Volume: 12; Journal Issue: 10]; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; Crystal structure; Dimers (Chemical physics); Histones; Sedimentation; Vector cloning; Crystals; Dimerization; Ultracentrifugation

Citation Formats

Aik, Wei Shen, Lin, Min-Han, Tan, Dazhi, Tripathy, Ashutosh, Marzluff, William F., Dominski, Zbigniew, Chou, Chi-Yuan, and Tong, Liang. The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3’-end processing. United States: N. p., 2017. Web. doi:10.1371/journal.pone.0186034.
Aik, Wei Shen, Lin, Min-Han, Tan, Dazhi, Tripathy, Ashutosh, Marzluff, William F., Dominski, Zbigniew, Chou, Chi-Yuan, & Tong, Liang. The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3’-end processing. United States. doi:10.1371/journal.pone.0186034.
Aik, Wei Shen, Lin, Min-Han, Tan, Dazhi, Tripathy, Ashutosh, Marzluff, William F., Dominski, Zbigniew, Chou, Chi-Yuan, and Tong, Liang. Wed . "The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3’-end processing". United States. doi:10.1371/journal.pone.0186034. https://www.osti.gov/servlets/purl/1430295.
@article{osti_1430295,
title = {The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3’-end processing},
author = {Aik, Wei Shen and Lin, Min-Han and Tan, Dazhi and Tripathy, Ashutosh and Marzluff, William F. and Dominski, Zbigniew and Chou, Chi-Yuan and Tong, Liang},
abstractNote = {Unlike canonical pre-mRNAs, animal replication-dependent histone pre-mRNAs lack introns and are processed at the 3’-end by a mechanism distinct from cleavage and polyadenylation. They have a 3’ stem loop and histone downstream element (HDE) that are recognized by stem-loop binding protein (SLBP) and U7 snRNP, respectively. The N-terminal domain (NTD) of Lsm11, a component of U7 snRNP, interacts with FLASH NTD and these two proteins recruit the histone cleavage complex containing the CPSF-73 endonuclease for the cleavage reaction. Here, we determined crystal structures of FLASH NTD and found that it forms a coiled-coil dimer. Using solution light scattering, we characterized the stoichiometry of the FLASH NTD-Lsm11 NTD complex and found that it is a 2:1 heterotrimer, which is supported by observations from analytical ultracentrifugation and crosslinking.},
doi = {10.1371/journal.pone.0186034},
journal = {PLoS ONE},
number = [10],
volume = [12],
place = {United States},
year = {2017},
month = {10}
}

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