Theoretical studies on RNA recognition by Musashi 1 RNA-binding protein

Darai, Nitchakan and Mahalapbutr, Panupong and Wolschann, Peter and Lee, Vannajan Sanghiran and Wolfinger, Michael T. and Rungrotmongkol, Thanyada (2022) Theoretical studies on RNA recognition by Musashi 1 RNA-binding protein. Scientific Reports, 12 (1). ISSN 2045-2322, DOI

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The Musashi (MSI) family of RNA-binding proteins, comprising the two homologs Musashi-1 (MSI1) and Musashi-2 (MSI2), typically regulates translation and is involved in cell proliferation and tumorigenesis. MSI proteins contain two ribonucleoprotein-like RNA-binding domains, RBD1 and RBD2, that bind single-stranded RNA motifs with a central UAG trinucleotide with high affinity and specificity. The finding that MSI also promotes the replication of Zika virus, a neurotropic Flavivirus, has triggered further investigations of the biochemical principles behind MSI-RNA interactions. However, a detailed molecular understanding of the specificity of MSI RBD1/2 interaction with RNA is still missing. Here, we performed computational studies of MSI1-RNA association complexes, investigating different RNA pentamer motifs using molecular dynamics simulations with binding free energy calculations based on the solvated interaction energy method. Simulations with Alphafold2 suggest that predicted MSI protein structures are highly similar to experimentally determined structures. The binding free energies show that two out of four RNA pentamers exhibit a considerably higher binding affinity to MSI1 RBD1 and RBD2, respectively. The obtained structural information on MSI1 RBD1 and RBD2 will be useful for a detailed functional and mechanistic understanding of this type of RNA-protein interactions.

Item Type: Article
Funders: Second Century Fund (C2F), Chulalongkorn Universit, National Research Council of Thailand (NRCT) [Grant No; NRCT5-RGJ63001-009], 90th anniversary of CU Fund (Ratchadaphiseksomphot Endowment Fund) [Grant No; GCUGR1125651012D], ASEAN-European Academic University Network (ASEA-UNINET)
Uncontrolled Keywords: Solvated interaction energy; Molecular-dynamics; Regulator; Sequence; Domain; SIE
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 19 Oct 2023 07:56
Last Modified: 19 Oct 2023 07:56

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