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July 17th, 2025
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UNC Chapel Hill
molecular biology
biorxiv

Correlated protein-RNA associations reveal a requirement for HNRNPU in long-range Polycomb recruitment by the lncRNAs Airn, Kcnq1ot1, and Xist

Murvin, M. M.Open in Google Scholar•Li, S.Open in Google Scholar•Boyson, S.Open in Google Scholar•Zhang, Z.Open in Google Scholar•Cherney, R. E.Open in Google Scholar•Calabrese, M.Open in Google Scholar

The lncRNAs Airn, Kcnq1ot1, and Xist recruit Polycomb Repressive Complexes (PRCs) and repress genes over multi-megabase genomic regions, but how they interact with proteins to carry out repression remain poorly understood. To investigate, we conducted RNA-immunoprecipitations from formaldehyde-crosslinked mouse trophoblast stem cells, using antibodies against 27 proteins known to associate with Xist. Relative to other chromatin-bound transcripts, Airn, Kcnq1ot1, and Xist exhibited enriched and highly correlated associations with several RNA-binding proteins. The degree of repression induced by Airn, Kcnq1ot1, and Xist unexpectedly correlated with the extent to which the lncRNAs partitioned protein associations into communities. HNRNPU, a chromatin-associated RNA-binding protein, exhibited enriched association with, and was required to induce PRC-directed modifications by, all three lncRNAs, without being necessary for proper localization of Airn or Kcnq1ot1. Our data nominate multivalent RNA-protein interaction domains, along with the chromatin-associated RNA-binding protein HNRNPU, as features important for long-range gene regulation induced by chromatin-associated RNAs.

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