ArticleBiochemistry2010
Dynamic origins of differential RNA binding function in two dsRBDs from the miRNA "microprocessor" complex.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Regulation of the microprocessor by post-translational modifications.Frontiers in cell and developmental biology · 2025Review
- The Functional Mechanism of MicroRNA in Oral Lichen Planus.Journal of inflammation research · 2022Review
- Elucidating the Role of Microprocessor Protein DGCR8 in Bending RNA Structures.Biophysical journal · 2020Article
- The Functional Cycle of Rnt1p: Five Consecutive Steps of Double-Stranded RNA Processing by a Eukaryotic RNase III.Structure (London, England : 1993) · 2017Article
- Article
- Binding by TRBP-dsRBD2 Does Not Induce Bending of Double-Stranded RNA.Biophysical journal · 2016Article
- Noncoding RNA as regulators of cardiac fibrosis: current insight and the road ahead.Pflugers Archiv : European journal of physiology · 2016Review
- Article
- Article
- Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile.Cell reports · 2013Article
- Thermodynamic and structural determinants of differential Pdx1 binding to elements from the insulin and IAPP promoters.Journal of molecular biology · 2013Article
- The core microprocessor component DiGeorge syndrome critical region 8 (DGCR8) is a nonspecific RNA-binding protein.The Journal of biological chemistry · 2013Article
- The RNA-binding region of human TRBP interacts with microRNA precursors through two independent domains.Nucleic acids research · 2013Article
- Ensemble analysis of primary microRNA structure reveals an extensive capacity to deform near the Drosha cleavage site.Biochemistry · 2013Article
- Current approaches to micro-RNA analysis and target gene prediction.Journal of applied genetics · 2012Review
- Article
- Ribonuclease III mechanisms of double-stranded RNA cleavage.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
MicroRNAs (miRNAs) affect gene regulation by base pairing with mRNA and contribute to the control of cellular homeostasis. The first step in miRNA maturation is conducted in the nucleus by the "microprocessor" complex made up of an RNase III enzyme, Drosha, that contains one dsRNA binding domain (dsRBD), and DGCR8, that contains two dsRBDs in tandem. The crystal structure of DGCR8-Core (493-720), containing both dsRBDs, and the NMR solution structure of Drosha-dsRBD (1259-1337) have been reported, but the solution dynamics have not been explored for any of these dsRBDs. To better define the mechanism of dsRNA binding and thus the nuclear maturation step of miRNA processing, we report NMR spin relaxation and MD simulations of Drosha-dsRBD (1259-1337) and DGCR8-dsRBD1 (505-583). The study was motivated by electrophoretic mobility shift assays (EMSAs) of the two dsRBDs, which showed that Drosha-dsRBD does not bind a representative miRNA but isolated DGCR8-dsRBD1 does (K(d) = 9.4 ± 0.4 μM). Our results show that loop 2 in both dsRBDs is highly dynamic but the pattern of the correlations observed in MD is different for the two proteins. Additionally, the extended loop 1 of Drosha-dsRBD is more flexible than the corresponding loop in DGCR8-dsRBD1 but shows no correlation with loop 2, which potentially explains the lack of dsRNA binding by Drosha-dsRBD in the absence of the RNase III domains. The results presented in this study provide key structural and dynamic features of dsRBDs that contribute to the binding mechanism of these domains to dsRNA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.