Searching across hundreds of databases
Molecules capable of directing changes to nucleic acid sequences are powerful tools for molecular biology and promising candidates for the therapeutic correction of disease-causing mutations. However, unwanted reactions at off-target sites complicate their use. Here we report selective combinations of mutant editing enzyme and directing oligonucleotide. Mutations in human ADAR2 (adenosine deaminase acting on RNA 2) that introduce aromatic amino acids at position 488 reduce background RNA editing. This residue is juxtaposed to the nucleobase that pairs with the editing site adenine, suggesting a steric clash for the bulky mutants. Replacing this nucleobase with a hydrogen atom removes the clash and restores editing activity. A crystal structure of the E488Y mutant bound to abasic site-containing RNA shows the accommodation of the tyrosine side chain. Finally, we demonstrate directed RNA editing in vitro and in human cells using mutant ADAR2 proteins and modified guide RNAs with reduced off-target activity.
Pubmed ID: 30581135 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsSoftware for automatic general image analysis. It provides fully automatic analysis of 1-D gels including lane creation, background subtraction, band detection, molecular weight calibration, quantity calibration, and normalization. Editing tools are provided for cropping, rotating, and filtering images.
View all literature mentionsSoftware for x-ray detection and processing single-crystal monochromatic diffraction data recorded by the rotation method. XDS can process data images from CCD-, imaging-plate-, multiwire-, and pixel-detectors in a variety of formats.
View all literature mentionsThe Global Proteome Machine Organization was set up so that scientists involved in proteomics using tandem mass spectrometry could use that data to analyze proteomes. The projects supported by the GPMO have been selected to improve the quality of analysis, make the results portable and to provide a common platform for testing and validating proteomics results. The Global Proteome Machine Database was constructed to utilize the information obtained by GPM servers to aid in the difficult process of validating peptide MS/MS spectra as well as protein coverage patterns. This database has been integrated into GPM server pages, allowing users to quickly compare their experimental results with the best results that have been previously observed by other scientists.
View all literature mentionsPortal for Macromolecular X-Ray Crystallography to produce and support an integrated suite of programs that allows researchers to determine macromolecular structures by X-ray crystallography, and other biophysical techniques. Used in the education and training of scientists in experimental structural biology for determination and analysis of protein structure.
View all literature mentionsThis monoclonal targets HA Tag
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets HA Tag
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
