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Staufen1 (STAU1) is a dsRNA binding protein mediating mRNA transport and localization, translational control and STAU1-mediated mRNA decay (SMD). The STAU1 binding site (SBS) within human ADP-ribosylation factor1 (ARF1) 3'UTR binds STAU1 and this downregulates ARF1 cytoplasmic mRNA levels by SMD. However, how STAU1 recognizes specific mRNA targets is still under debate. Our structure of the ARF1 SBS-STAU1 complex uncovers target recognition by STAU1. STAU1 dsRNA binding domain (dsRBD) 4 interacts with two pyrimidines and one purine from the minor groove side via helix α1, the β1-β2 loop anchors the dsRBD at the end of the dsRNA and lysines in helix α2 bind to the phosphodiester backbone from the major groove side. STAU1 dsRBD3 displays the same binding mode with specific recognition of one guanine base. Mutants disrupting minor groove recognition of ARF1 SBS affect in vitro binding and reduce SMD in vivo. Our data thus reveal how STAU1 recognizes minor groove features in dsRNA relevant for target selection.
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http://dx.doi.org/10.1093/nar/gkz1163 | DOI Listing |
Eur J Med Chem
August 2025
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China. Electronic address:
Pyrrolobenzodiazepine (PBD) dimers constitute a class of highly cytotoxic agents that induce apoptosis through the formation of effective DNA interstrand cross-links by binding to the minor groove of DNA. This mechanism highlights the critical role of PBD dimers in the development of antibody-drug conjugates (ADCs). Within ADCs, PBD dimers act as potent payloads that are specifically delivered to cancer cells via monoclonal antibodies, thereby enhancing therapeutic efficacy while minimizing collateral damage to normal tissues.
View Article and Find Full Text PDFJ Proteome Res
September 2025
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.
Prostate cancer (PCa) remains a major global health concern, ranking among the most prevalent cancer in men worldwide. Despite the availability of various therapeutic options, the clinical efficacy of current anti-PCa agents is often compromised by drug resistance and adverse effects. DNA minor groove binders offer a potential therapeutic alternative, owing to their selective mechanism of action and favorable safety profiles.
View Article and Find Full Text PDFRSC Adv
August 2025
Department of Chemistry, Faculty of Science, Islamic University of Madinah Madinah 42351 Saudi Arabia.
Cancer continues to be a major global health challenge, necessitating the ongoing development of novel small-molecule therapeutics that can selectively target DNA and disrupt cancer cell proliferation. In this study we report the synthesis and characterization of novel guanidine derivatives (7a-j). Their DNA-binding potential was assessed through electronic absorption spectroscopy, revealing characteristic hypochromic shifts indicative of minor groove-binding interactions with salmon sperm DNA (SS-DNA).
View Article and Find Full Text PDFRSC Med Chem
July 2025
Microbiota Research Center, Istinye University Istanbul 34010 Turkey.
Due to limited advances in diagnosis and targeted therapy, as well as poor understanding of pathophysiology, infections due to have remained a medical concern. With their ability to selectively bind to DNA sequences, minor groove binders have emerged as useful therapeutic agents against parasitic infections. Herein, 6 novel thiazole-based minor groove binders were synthesized.
View Article and Find Full Text PDFJ Phys Chem B
September 2025
Department of Physics and Mathematics, Institute of Chemistry, São Paulo State University (UNESP), Araraquara, São Paulo 14800-060, Brazil.
Magnesium ions (Mg) play a crucial role in stabilizing various RNA tertiary motifs, such as pseudoknots, G-quadruplexes, kissing loops, and A-minor motifs, to name a few. Despite their importance, the precise location and role of Mg ions in RNA folding are challenging to characterize both experimentally and computationally. In this study, we employ an all-atom structure-based model integrated with the dynamic counterion condensation (DCC) model to investigate the folding and unfolding transitions of apo SAM-II riboswitch RNA at physiological concentrations of Mg.
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