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Here, we develop INSCRIBE (<jats:underline>IN<\/jats:underline> situ <jats:underline>S<\/jats:underline>ensitive <jats:underline>C<\/jats:underline>apture of <jats:underline>R<\/jats:underline>NA-protein <jats:underline>I<\/jats:underline>nteractions in <jats:underline>B<\/jats:underline>iological <jats:underline>E<\/jats:underline>nvironments), circumventing the challenges through in situ RNA labeling by precisely directing a purified APOBEC1-nanobody fusion to the RBP of interest. This method enables highly specific RNA-binding site identification across a diverse range of fixed biological samples such as HEK293T cells and mouse brain tissue and accurately identifies the canonical binding motifs of RBFOX2 (UGCAUG) and TDP-43 (UGUGUG) in native cellular environments. Applicable to any RBP with available primary antibodies, INSCRIBE enables sensitive capture of RBP-RNA interactions from ultra-low input equivalent to ~5 cells. The robust, versatile, and sensitive INSCRIBE workflow is particularly beneficial for precious tissues such as clinical samples, empowering the exploration of genuine RBP-RNA interactions in RNA-related disease contexts.<\/jats:p>","DOI":"10.1038\/s41467-024-50363-4","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T13:02:35Z","timestamp":1723813355000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["High-sensitivity in situ capture of endogenous RNA-protein interactions in fixed cells and primary tissues"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4351-3140","authenticated-orcid":false,"given":"Qishan","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7753-7741","authenticated-orcid":false,"given":"Tao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Kofman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0257-3139","authenticated-orcid":false,"given":"Pratibha","family":"Jagannatha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Rhine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5615-8550","authenticated-orcid":false,"given":"Brian A.","family":"Yee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Corbett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0799-6037","authenticated-orcid":false,"given":"Gene W.","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"50363_CR1","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/nrg3813","volume":"15","author":"S Gerstberger","year":"2014","unstructured":"Gerstberger, S., Hafner, M. & Tuschl, T. 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G.W.Y. is a distinguished visiting professor at the National University of Singapore. G.W.Y.\u2019s interests have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. The authors declare no other competing financial or non-financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7067"}}