{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:06:12Z","timestamp":1789175172014,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,8]]},"group-title":"Biophysics","reference-count":36,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R35GM151111"],"award-info":[{"award-number":["R35GM151111"]}]},{"award":["DAF2022-250422"],"award-info":[{"award-number":["DAF2022-250422"]}],"id":[{"id":"https:\/\/ror.org\/02qenvm24","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001341","name":"Richard and Susan Smith Family Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001341","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000008","name":"David and Lucile Packard Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000008","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  RNA structure can be predicted from sequence in dilute solution, but these predictions often fail in cells. Many cellular RNAs keep their\n                  <jats:italic>in vitro<\/jats:italic>\n                  folds, whereas others are substantially less structured. We combined single-molecule FRET with\n                  <jats:italic>Xenopus<\/jats:italic>\n                  oocyte extract to measure RNA folding and duplex formation under cell-like conditions. Extract proteins passively suppressed base pairing: they slowed apparent strand association while leaving duplex dissociation largely unchanged, without sequence specificity or ATP consumption. A competitive binding model captured this activity as an effective folding penalty of \u223c0.45 kcal\/mol per nucleotide. Similar activity occurred in HeLa lysate. Applied to in-cell chemical probing data, this correction stratified reactivity across \u223c42,000 stem-loops, whereas predictive models established in dilute solution classified nearly all as stably folded. Our results identify a passive protein-mediated mechanism as a key contributor to cellular RNA folding, shifting the balance between paired and unpaired states without changing the underlying base-pairing rules.\n                <\/jats:p>","DOI":"10.64898\/2026.09.07.749977","type":"posted-content","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:25:12Z","timestamp":1788927912000},"source":"Crossref","is-referenced-by-count":0,"title":["A passive protein environment offsets RNA folding energetics in cells"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6627-5283","authenticated-orcid":false,"given":"M.","family":"Todisco","sequence":"first","affiliation":[{"name":"Whitehead Institute for Biomedical Research; Cambridge, MA, 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7663-2408","authenticated-orcid":false,"given":"F.","family":"Boskovic","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Chicago; Chicago, IL, 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Jain","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research; Cambridge, MA, 02142, USA"},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091117105565000_2026.09.07.749977v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp892"},{"key":"2026091117105565000_2026.09.07.749977v1.2","doi-asserted-by":"crossref","unstructured":"R. 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