Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding
Abstract PUF proteins are characterized by globular RNA-binding domains. They also interact with partner proteins that modulate their RNA-binding activities. Caenorhabditis elegans PUF protein fem-3 binding factor-2 (FBF-2) partners with intrinsically disordered Lateral Signaling Target-1 (LST-1) to...
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Nature Portfolio
2023-11-01
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Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-023-43098-1 |
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author | Chen Qiu Zihan Zhang Robert N. Wine Zachary T. Campbell Jun Zhang Traci M. Tanaka Hall |
author_facet | Chen Qiu Zihan Zhang Robert N. Wine Zachary T. Campbell Jun Zhang Traci M. Tanaka Hall |
author_sort | Chen Qiu |
collection | DOAJ |
description | Abstract PUF proteins are characterized by globular RNA-binding domains. They also interact with partner proteins that modulate their RNA-binding activities. Caenorhabditis elegans PUF protein fem-3 binding factor-2 (FBF-2) partners with intrinsically disordered Lateral Signaling Target-1 (LST-1) to regulate target mRNAs in germline stem cells. Here, we report that an intrinsically disordered region (IDR) at the C-terminus of FBF-2 autoinhibits its RNA-binding affinity by increasing the off rate for RNA binding. Moreover, the FBF-2 C-terminal region interacts with its globular RNA-binding domain at the same site where LST-1 binds. This intramolecular interaction restrains an electronegative cluster of amino acid residues near the 5′ end of the bound RNA to inhibit RNA binding. LST-1 binding in place of the FBF-2 C-terminus therefore releases autoinhibition and increases RNA-binding affinity. This regulatory mechanism, driven by IDRs, provides a biochemical and biophysical explanation for the interdependence of FBF-2 and LST-1 in germline stem cell self-renewal. |
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language | English |
last_indexed | 2024-03-10T17:24:12Z |
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spelling | doaj.art-3607db53874c45c8bec3e4e18e25da6f2023-11-20T10:14:46ZengNature PortfolioNature Communications2041-17232023-11-0114111310.1038/s41467-023-43098-1Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA bindingChen Qiu0Zihan Zhang1Robert N. Wine2Zachary T. Campbell3Jun Zhang4Traci M. Tanaka Hall5Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthDepartment of Chemistry, University of Alabama at BirminghamEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthDepartment of Anesthesiology, University of Wisconsin School of Medicine and Public HealthDepartment of Chemistry, University of Alabama at BirminghamEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthAbstract PUF proteins are characterized by globular RNA-binding domains. They also interact with partner proteins that modulate their RNA-binding activities. Caenorhabditis elegans PUF protein fem-3 binding factor-2 (FBF-2) partners with intrinsically disordered Lateral Signaling Target-1 (LST-1) to regulate target mRNAs in germline stem cells. Here, we report that an intrinsically disordered region (IDR) at the C-terminus of FBF-2 autoinhibits its RNA-binding affinity by increasing the off rate for RNA binding. Moreover, the FBF-2 C-terminal region interacts with its globular RNA-binding domain at the same site where LST-1 binds. This intramolecular interaction restrains an electronegative cluster of amino acid residues near the 5′ end of the bound RNA to inhibit RNA binding. LST-1 binding in place of the FBF-2 C-terminus therefore releases autoinhibition and increases RNA-binding affinity. This regulatory mechanism, driven by IDRs, provides a biochemical and biophysical explanation for the interdependence of FBF-2 and LST-1 in germline stem cell self-renewal.https://doi.org/10.1038/s41467-023-43098-1 |
spellingShingle | Chen Qiu Zihan Zhang Robert N. Wine Zachary T. Campbell Jun Zhang Traci M. Tanaka Hall Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding Nature Communications |
title | Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding |
title_full | Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding |
title_fullStr | Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding |
title_full_unstemmed | Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding |
title_short | Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding |
title_sort | intra and inter molecular regulation by intrinsically disordered regions governs puf protein rna binding |
url | https://doi.org/10.1038/s41467-023-43098-1 |
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