ArticlePloS one2014
Bioenergetics and gene silencing approaches for unraveling nucleotide recognition by the human EIF2C2/Ago2 PAZ domain.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
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- DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review.International journal of molecular sciences · 2021Review
- Circulating microRNA trafficking and regulation: computational principles and practice.Briefings in bioinformatics · 2020Review
- RNA Secondary Structure Motifs of the Influenza A Virus as Targets for siRNA-Mediated RNA Interference.Molecular therapy. Nucleic acids · 2020Article
- Label-Free Electrophoretic Mobility Shift Assay (EMSA) for Measuring Dissociation Constants of Protein-RNA Complexes.Current protocols in nucleic acid chemistry · 2019Article
- Evidence for Ion-Templation During Macrocyclooligomerization of Depsipeptides.Journal of the American Chemical Society · 2018Article
- Regulation of insulin resistance and type II diabetes by hepatitis C virus infection: A driver function of circulating miRNAs.Journal of cellular and molecular medicine · 2018Review
- Exploring PAZ/3'-overhang interaction to improve siRNA specificity. A combined experimental and modeling study.Chemical science · 2018Article
- Genome-Wide DNA Methylation Study Identifies Significant Epigenomic Changes in Osteoarthritic Subchondral Bone and Similarity to Overlying Cartilage.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- Human Absorbable MicroRNA Prediction based on an Ensemble Manifold Ranking Model.Proceedings. IEEE International Conference on Bioinformatics and Biomedicine · 2015Article
- EIF2C, Dicer, and Drosha are up-regulated along tumor progression and associated with poor prognosis in bladder carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene silencing and RNA interference are major cellular processes that control gene expression via the cleavage of target mRNA. Eukaryotic translation initiation factor 2C2 (EIF2C2, Argonaute protein 2, Ago2) is considered to be the major player of RNAi as it is the core component of RISC complexes. While a considerable amount of research has focused on RNA interference and its associated mechanisms, the nature and mechanisms of nucleotide recognition by the PAZ domain of EIF2C2/Ago2 have not yet been characterized. Here, we demonstrate that the EIF2C2/Ago2 PAZ domain has an inherent lack of binding to adenine nucleotides, a feature that highlights the poor binding of 3'-adenylated RNAs with the PAZ domain as well as the selective high trimming of the 3'-ends of miRNA containing adenine nucleotides. We further show that the PAZ domain selectively binds all ribonucleotides (except adenosine), whereas it poorly recognizes deoxyribonucleotides. In this context, the modification of dTMP to its ribonucleotide analogue gave a drastic improvement of binding enthalpy and, hence, binding affinity. Additionally, higher in vivo gene silencing efficacy was correlated with the stronger PAZ domain binders. These findings provide new insights into the nature of the interactions of the EIF2C2/Ago2 PAZ domain.
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