Molecular basis for the distinct cellular functions of the Lsm1–7 and Lsm2–8 complexes

Montemayor, Eric J.; Virta, Johanna M.; Hayes, Samuel M.; Nomura, Yuichiro; Brow, David A.; Butcher, Samuel E.

doi:10.1261/rna.075879.120

Molecular basis for the distinct cellular functions of the Lsm1–7 and Lsm2–8 complexes

Journal Article · Tue Jun 09 00:00:00 EDT 2020 · RNA

DOI:https://doi.org/10.1261/rna.075879.120· OSTI ID:1682317

^[1]; Virta, Johanna M. ^[1]; Hayes, Samuel M. ^[1]; ^[1]; ^[1]; ^[1]

Univ. of Wisconsin, Madison, WI (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); National Science Foundation (NSF); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1682317

Journal Information:: RNA, Journal Name: RNA Journal Issue: 10 Vol. 26; ISSN 1355-8382

Publisher:: Cold Spring Harbor Laboratory PressCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Additional file 1 of Hcp2a of APEC affects mRNA splicing and protein quality control in DF-1 cells Song, Xiangjun; Chen, Zhe; Li, Ziqi figshare https://doi.org/10.6084/m9.figshare.21102161.v1	dataset	January 2022
Additional file 2 of Hcp2a of APEC affects mRNA splicing and protein quality control in DF-1 cells Song, Xiangjun; Chen, Zhe; Li, Ziqi figshare https://doi.org/10.6084/m9.figshare.21102164	dataset	January 2022
Additional file 3 of Hcp2a of APEC affects mRNA splicing and protein quality control in DF-1 cells Song, Xiangjun; Chen, Zhe; Li, Ziqi figshare https://doi.org/10.6084/m9.figshare.21102167	dataset	January 2022

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59 BASIC BIOLOGICAL SCIENCES
Lsm1–7
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RNA binding proteins
U6 snRNA
X-ray crystallography

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