Comparative analysis of the LARP1 C-terminal DM15 region through Coelomate evolution.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Ribonucleoproteins*/metabolism ; Ribonucleoproteins*/genetics ; Ribonucleoproteins*/chemistry ; SS-B Antigen* ; Autoantigens*/metabolism ; Autoantigens*/genetics ; Autoantigens*/chemistry ; Evolution, Molecular*; Animals ; Humans ; Zebrafish/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Molecular Dynamics Simulation ; Amino Acid Sequence ; Protein Binding

TOR (target of rapamycin), a ubiquitous protein kinase central to cellular homeostasis maintenance, fundamentally regulates ribosome biogenesis in part by its target La-related protein 1 (LARP1). Among other target transcripts, LARP1 specifically binds TOP (terminal oligopyrimidine) mRNAs encoding all 80 ribosomal proteins in a TOR-dependent manner through its C-terminal region containing the DM15 module. Though the functional implications of the LARP1 interaction with target mRNAs is controversial, it is clear that the TOP-LARP1-TOR axis is critical to cellular health in humans. Its existence and role in evolutionarily divergent animals remain less understood. We focused our work on expanding our knowledge of the first arm of the axis: the connection between LARP1-DM15 and the 5' TOP motif. We show that the overall DM15 architecture observed in humans is conserved in fruit fly and zebrafish. Both adopt familiar curved arrangements of HEAT-like repeats that bind 5' TOP mRNAs on the same conserved surface, although molecular dynamics simulations suggest that the N-terminal fold of the fruit fly DM15 is predicted to be unstable and unfold. We demonstrate that each ortholog interacts with TOP sequences with varying affinities. Importantly, we determine that the ability of the DM15 region to bind some TOP sequences but not others might amount to the context of the RNA structure, rather than the ability of the module to recognize some sequences but not others. We propose that TOP mRNAs may retain similar secondary structures to regulate LARP1 DM15 recognition.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (Ribonucleoproteins)
0 (SS-B Antigen)
0 (Autoantigens)
0 (RNA, Messenger)

Date Created: 20240827 Date Completed: 20240827 Latest Revision: 20240830

20240830

PMC11349179

10.1371/journal.pone.0308574

39190712