The Drosophila RNA binding protein Hrp48 binds a specific RNA sequence of the msl-2 mRNA 3' UTR to regulate translation
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- dc.contributor.author Lomoschitz, Andrea
- dc.contributor.author Meyer, Julia
- dc.contributor.author Guitart, Tanit
- dc.contributor.author Krepl, Miroslav
- dc.contributor.author Lapouge, Karine
- dc.contributor.author Hayn, Clara
- dc.contributor.author Schweimer, Kristian
- dc.contributor.author Simon, Bernd
- dc.contributor.author Šponer, Jiří
- dc.contributor.author Gebauer, Fátima
- dc.contributor.author Hennig, Janosch
- dc.date.accessioned 2025-01-22T07:23:26Z
- dc.date.available 2025-01-22T07:23:26Z
- dc.date.issued 2025
- dc.description.abstract Repression of msl-2 mRNA translation is essential for viability of Drosophila melanogaster females to prevent hypertranscription of both X chromosomes. This translational control event is coordinated by the female-specific protein Sex-lethal (Sxl) which recruits the RNA binding proteins Unr and Hrp48 to the 3' untranslated region (UTR) of the msl-2 transcript and represses translation initiation. The mechanism exerted by Hrp48 during translation repression and its interaction with msl-2 are not well understood. Here we investigate the RNA binding specificity and affinity of the tandem RNA recognition motifs of Hrp48. Using NMR spectroscopy, molecular dynamics simulations and isothermal titration calorimetry, we identified the exact region of msl-2 3' UTR recognized by Hrp48. Additional biophysical experiments and translation assays give further insights into complex formation of Hrp48, Unr, Sxl and RNA. Our results show that Hrp48 binds independent of Sxl and Unr downstream of the E and F binding sites of Sxl and Unr to msl-2.
- dc.description.sponsorship We thank the local contacts at DESY Hamburg PETRA-3 (P12 beamline) for support J.Š. and M.K. acknowledge support of the Czech Science Foundation (grant number 23-05639S). F.G. acknowledges support from the Spanish Ministry of Science and Innovation (MCIN) (grant PID2021-127948NB-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER, UE) and the Catalan Agency for Research and Universities (SGR-Cat-2021-01215). J.H. gratefully acknowledges support from the Deutsche Forschungsgemeinschaft (DFG, HE 7291/5-1).
- dc.format.mimetype application/pdf
- dc.identifier.citation Lomoschitz A, Meyer J, Guitart T, Krepl M, Lapouge K, Hayn C, et al. The Drosophila RNA binding protein Hrp48 binds a specific RNA sequence of the msl-2 mRNA 3' UTR to regulate translation. Biophys Chem. 2025 Jan;316:107346. DOI: 10.1016/j.bpc.2024.107346
- dc.identifier.doi http://dx.doi.org/10.1016/j.bpc.2024.107346
- dc.identifier.issn 0301-4622
- dc.identifier.uri http://hdl.handle.net/10230/69229
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Biophys Chem. 2025 Jan;316:107346
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-127948NB-I00
- dc.rights © 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Dosage compensation
- dc.subject.keyword Hrp48
- dc.subject.keyword RNA binding protein
- dc.subject.keyword RNA recognition motif
- dc.subject.keyword Translation regulation
- dc.title The Drosophila RNA binding protein Hrp48 binds a specific RNA sequence of the msl-2 mRNA 3' UTR to regulate translation
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion