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ArticleVolume 86, Issue 14p2811-2827.e10Open access Affiliations & Notes 1Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, 92093, United States of America 2Sanford Stem Cell Institution Innovation Center, Stem Cell Program, University of California, San Diego, La Jolla, CA, 92037, United States of America 3Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, 92093, United States of America 4Bioinformatics and...
Abstract The brain displays the richest repertoire of post-transcriptional mechanisms regulating mRNA translation1,2,3,4,5,6,7,8,9,10,11. Among these, alternative splicing has been shown to drive cell-type specificity and, when disrupted, is strongly linked to neurological disorders12,13,14,15,16,17. However, genome-wide measurements of mRNA translation with isoform sensitivity at single-cell resolution have not been achieved.
Abstract RNA-binding proteins (RBPs) have pivotal functions in RNA metabolism, but current methods are limited in retrieving RBP-RNA interactions within endogenous biological contexts. Here, we develop INSCRIBE (IN situ Sensitive Capture of RNA-protein Interactions in Biological Environments), circumventing the challenges through in situ RNA labeling by precisely directing a purified APOBEC1-nanobody fusion to the RBP of interest.
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