Molecular basis for the distinct cellular functions of the Lsm1–7 and Lsm2–8 complexes
Abstract
Eukaryotes possess eight highly conserved Lsm (like Sm) proteins that assemble into circular, heteroheptameric complexes, bind RNA, and direct a diverse range of biological processes. Among the many essential functions of Lsm proteins, the cytoplasmic Lsm1–7 complex initiates mRNA decay, while the nuclear Lsm2–8 complex acts as a chaperone for U6 spliceosomal RNA. It has been unclear how these complexes perform their distinct functions while differing by only one out of seven subunits. Here, we elucidate the molecular basis for Lsm-RNA recognition and present four high-resolution structures of Lsm complexes bound to RNAs. The structures of Lsm2–8 bound to RNA identify the unique 2',3' cyclic phosphate end of U6 as a prime determinant of specificity. In contrast, the Lsm1–7 complex strongly discriminates against cyclic phosphates and tightly binds to oligouridylate tracts with terminal purines. Lsm5 uniquely recognizes purine bases, explaining its divergent sequence relative to other Lsm subunits. Lsm1–7 loads onto RNA from the 3' end and removal of the Lsm1 carboxy-terminal region allows Lsm1–7 to scan along RNA, suggesting a gated mechanism for accessing internal binding sites. These data reveal the molecular basis for RNA binding by Lsm proteins, a fundamental step in the formation of molecular assemblies thatmore »
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Institutes of Health (NIH); National Science Foundation (NSF)
- OSTI Identifier:
- 1682317
- Grant/Contract Number:
- AC02-06CH11357; P41 GM103403; S10 RR029205; 085P1000817; HHSN26120080001E; BIR-9512577; S10RR13790; R35 GM118075; R35 GM118131
- Resource Type:
- Accepted Manuscript
- Journal Name:
- RNA
- Additional Journal Information:
- Journal Volume: 26; Journal Issue: 10; Journal ID: ISSN 1355-8382
- Publisher:
- Cold Spring Harbor Laboratory Press
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Lsm1–7; Lsm2–8; RNA binding proteins; U6 snRNA; X-ray crystallography
Citation Formats
Montemayor, Eric J., Virta, Johanna M., Hayes, Samuel M., Nomura, Yuichiro, Brow, David A., and Butcher, Samuel E. Molecular basis for the distinct cellular functions of the Lsm1–7 and Lsm2–8 complexes. United States: N. p., 2020.
Web. doi:10.1261/rna.075879.120.
Montemayor, Eric J., Virta, Johanna M., Hayes, Samuel M., Nomura, Yuichiro, Brow, David A., & Butcher, Samuel E. Molecular basis for the distinct cellular functions of the Lsm1–7 and Lsm2–8 complexes. United States. https://doi.org/10.1261/rna.075879.120
Montemayor, Eric J., Virta, Johanna M., Hayes, Samuel M., Nomura, Yuichiro, Brow, David A., and Butcher, Samuel E. Tue .
"Molecular basis for the distinct cellular functions of the Lsm1–7 and Lsm2–8 complexes". United States. https://doi.org/10.1261/rna.075879.120. https://www.osti.gov/servlets/purl/1682317.
@article{osti_1682317,
title = {Molecular basis for the distinct cellular functions of the Lsm1–7 and Lsm2–8 complexes},
author = {Montemayor, Eric J. and Virta, Johanna M. and Hayes, Samuel M. and Nomura, Yuichiro and Brow, David A. and Butcher, Samuel E.},
abstractNote = {Eukaryotes possess eight highly conserved Lsm (like Sm) proteins that assemble into circular, heteroheptameric complexes, bind RNA, and direct a diverse range of biological processes. Among the many essential functions of Lsm proteins, the cytoplasmic Lsm1–7 complex initiates mRNA decay, while the nuclear Lsm2–8 complex acts as a chaperone for U6 spliceosomal RNA. It has been unclear how these complexes perform their distinct functions while differing by only one out of seven subunits. Here, we elucidate the molecular basis for Lsm-RNA recognition and present four high-resolution structures of Lsm complexes bound to RNAs. The structures of Lsm2–8 bound to RNA identify the unique 2',3' cyclic phosphate end of U6 as a prime determinant of specificity. In contrast, the Lsm1–7 complex strongly discriminates against cyclic phosphates and tightly binds to oligouridylate tracts with terminal purines. Lsm5 uniquely recognizes purine bases, explaining its divergent sequence relative to other Lsm subunits. Lsm1–7 loads onto RNA from the 3' end and removal of the Lsm1 carboxy-terminal region allows Lsm1–7 to scan along RNA, suggesting a gated mechanism for accessing internal binding sites. These data reveal the molecular basis for RNA binding by Lsm proteins, a fundamental step in the formation of molecular assemblies that are central to eukaryotic mRNA metabolism.},
doi = {10.1261/rna.075879.120},
journal = {RNA},
number = 10,
volume = 26,
place = {United States},
year = {Tue Jun 09 00:00:00 EDT 2020},
month = {Tue Jun 09 00:00:00 EDT 2020}
}
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