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We conducted formaldehyde-based RNA-immunoprecipitations (RIPs) of 27 proteins from mouse trophoblast stem cells (TSCs), using a protocol exhibiting similar signal-to-non-specific signal and post-lysis reassociation ratios as crosslinking immunoprecipitation (CLIP) and crosslinking affinity purification (CLAP). Patterns of protein associations across\n                    <jats:italic>Airn<\/jats:italic>\n                    and\n                    <jats:italic>Kcnq1ot1<\/jats:italic>\n                    were more similar to each other than to nearly all other transcripts and partitioned to extents that mirrored the degree of repression each lncRNA induced, implying connections to mechanism. Indeed, HNRNPU, a factor essential for\n                    <jats:italic>Xist<\/jats:italic>\n                    \u2019s localization to chromatin, was enriched over\n                    <jats:italic>Airn<\/jats:italic>\n                    and\n                    <jats:italic>Kcnq1ot1<\/jats:italic>\n                    and required to maintain normal levels of PRC1- and PRC2-directed chromatin modifications across the\n                    <jats:italic>Airn<\/jats:italic>\n                    and\n                    <jats:italic>Kcnq1ot1<\/jats:italic>\n                    target domains, yet was dispensable for both lncRNAs\u2019 localization to chromatin and for their association with PRC1. HNRNPU depletion caused a greater reduction in PRC-directed chromatin modifications and gene repression across the inactive X and the\u2009~\u200915 Mb\n                    <jats:italic>Airn<\/jats:italic>\n                    target domain than across the\u2009~\u20093 Mb\n                    <jats:italic>Kcnq1ot1<\/jats:italic>\n                    domain. Perhaps relatedly, HNRNPU depletion significantly reduced the overall levels of\n                    <jats:italic>Xist<\/jats:italic>\n                    and\n                    <jats:italic>Airn<\/jats:italic>\n                    but not\n                    <jats:italic>Kcnq1ot1<\/jats:italic>\n                    . Our study reports architectures of protein association along\n                    <jats:italic>Airn<\/jats:italic>\n                    and\n                    <jats:italic>Kcnq1ot1<\/jats:italic>\n                    compared to the transcriptome at large, highlights shared and distinct features between the two lncRNAs, and provides new perspective on the role of HNRNPU in long-range chromatin regulation by lncRNAs.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012215","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:39:38Z","timestamp":1782236378000},"page":"e1012215","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Correlated protein-RNA associations and a requirement for HNRNPU in the long-range recruitment of Polycomb Repressive Complexes by the lncRNAs Airn and Kcnq1ot1"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2686-2691","authenticated-orcid":true,"given":"McKenzie M.","family":"Murvin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4658-9765","authenticated-orcid":true,"given":"Shuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7183-7516","authenticated-orcid":true,"given":"Elizabeth W.","family":"Abrash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget A.","family":"Peck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel P.","family":"Boyson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5739-4771","authenticated-orcid":true,"given":"Rachel E.","family":"Cherney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1213-2540","authenticated-orcid":true,"given":"J. 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