ArticleNucleic acids research2018
An engineered RNA binding protein with improved splicing regulation.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- MBNL proteins in health, disease, and therapeutic applications.Nucleic acids research · 2026Review
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- Strategies for programmable manipulation of alternative splicing.Current opinion in genetics & development · 2024Review
- Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes.Nature communications · 2023Article
- Automatic Text-Mining Approach to Identify Molecular Target Candidates Associated with Metabolic Processes for Myotonic Dystrophy Type 1.International journal of environmental research and public health · 2023Article
- Cognate RNA-Binding Modes by the Alternative-Splicing Regulator MBNL1 Inferred from Molecular Dynamics.International journal of molecular sciences · 2022Article
- The Role of RNA-Binding Proteins in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Alternative splicing diversifies the skeletal muscle transcriptome during prolonged spaceflight.Skeletal muscle · 2022Article
- The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians.PLoS biology · 2022Article
- Principles and pitfalls of high-throughput analysis of microRNA-binding thermodynamics and kinetics by RNA Bind-n-Seq.Cell reports methods · 2022Article
- Reversal of RNA toxicity in myotonic dystrophy via a decoy RNA-binding protein with high affinity for expanded CUG repeats.Nature biomedical engineering · 2022Article
- Disrupting the Molecular Pathway in Myotonic Dystrophy.International journal of molecular sciences · 2021Review
- The potential of engineered eukaryotic RNA-binding proteins as molecular tools and therapeutics.Wiley interdisciplinary reviews. RNA · 2020Review
- Non-invasive monitoring of alternative splicing outcomes to identify candidate therapies for myotonic dystrophy type 1.Nature communications · 2018Article
- MBNL splicing activity depends on RNA binding site structural context.Nucleic acids research · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The muscleblind-like (MBNL) family of proteins are key developmental regulators of alternative splicing. Sequestration of MBNL proteins by expanded CUG/CCUG repeat RNA transcripts is a major pathogenic mechanism in the neuromuscular disorder myotonic dystrophy (DM). MBNL1 contains four zinc finger (ZF) motifs that form two tandem RNA binding domains (ZF1-2 and ZF3-4) which each bind YGCY RNA motifs. In an effort to determine the differences in function between these domains, we designed and characterized synthetic MBNL proteins with duplicate ZF1-2 or ZF3-4 domains, referred to as MBNL-AA and MBNL-BB, respectively. Analysis of splicing regulation revealed that MBNL-AA had up to 5-fold increased splicing activity while MBNL-BB had 4-fold decreased activity compared to a MBNL protein with the canonical arrangement of zinc finger domains. RNA binding analysis revealed that the variations in splicing activity are due to differences in RNA binding specificities between the two ZF domains rather than binding affinity. Our findings indicate that ZF1-2 drives splicing regulation via recognition of YGCY RNA motifs while ZF3-4 acts as a general RNA binding domain. Our studies suggest that synthetic MBNL proteins with improved or altered splicing activity have the potential to be used as both tools for investigating splicing regulation and protein therapeutics for DM and other microsatellite diseases.
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Registered trials
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.