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Identification of RNA-binding proteins relies mainly on UV-induced crosslinking (UVX) followed by the enrichment of RNA\u2013protein conjugates and LC-MS\/MS analysis. However, UVX has limited applicability in tissues of multicellular organisms due to its low penetration depth. Here, we introduce formaldehyde crosslinking (FAX) as an alternative chemical crosslinking for RNA interactome capture (RIC). Mild FAX captures RNA\u2013protein interaction with high specificity and efficiency in cell culture. Unlike UVX-RIC, FAX-RIC robustly detects proteins that bind to structured RNAs or uracil-poor RNAs (e.g. AGO1, STAU1, UPF1, NCBP2, EIF4E, YTHDF proteins and PABP), broadening the coverage. Applied to Xenopus laevis oocytes and embryos, FAX-RIC provided comprehensive and unbiased RNA interactome, revealing dynamic remodeling of RNA\u2013protein complexes. Notably, translation machinery changes during oocyte-to-embryo transition, for instance, from canonical eIF4E to noncanonical eIF4E3. Furthermore, using Mus musculus liver, we demonstrate that FAX-RIC is applicable to mammalian tissue samples. Taken together, we report that FAX can extend the RNA interactome profiling into multicellular organisms.<\/jats:p>","DOI":"10.1093\/nar\/gkaa1194","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T00:16:14Z","timestamp":1606263374000},"page":"e28-e28","source":"Crossref","is-referenced-by-count":24,"title":["FAX-RIC enables robust profiling of dynamic RNP complex formation in multicellular organisms<i>in vivo<\/i>"],"prefix":"10.1093","volume":"49","author":[{"given":"Yongwoo","family":"Na","sequence":"first","affiliation":[{"name":"Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea"},{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea"},{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon","family":"Choi","sequence":"additional","affiliation":[{"name":"Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea"},{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanghee","family":"Shin","sequence":"additional","affiliation":[{"name":"Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea"},{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hun","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Kyung Hee University, Yongin 17104, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00a0Chul","family":"Kwon","sequence":"additional","affiliation":[{"name":"Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea"},{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3213-4965","authenticated-orcid":false,"given":"V Narry","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea"},{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-8440","authenticated-orcid":false,"given":"Jong-Seo","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea"},{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"2021031723315966400_B1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrm760","article-title":"Messenger-RNA-binding proteins and the messages they carry","volume":"3","author":"Dreyfuss","year":"2002","journal-title":"Nat. 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