{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T18:57:25Z","timestamp":1773687445075,"version":"3.50.1"},"reference-count":38,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"11","funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA240984"],"award-info":[{"award-number":["R01CA240984"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA244634"],"award-info":[{"award-number":["R01CA244634"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["1S10OD028511-01"],"award-info":[{"award-number":["1S10OD028511-01"]}]},{"name":"Era of Hope Scholar","award":["W81XWH-2210121"],"award-info":[{"award-number":["W81XWH-2210121"]}]},{"name":"Zena Werb Scholar","award":["T32CA108462"],"award-info":[{"award-number":["T32CA108462"]}]},{"name":"MD fellowship from the Boehringer Ingelheim Fonds"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,3,13]]},"abstract":"<jats:p>\n                    Heterogeneity in cancer gene expression is typically linked to genetic and epigenetic alterations, yet the extent of contribution from posttranscriptional regulation remains unclear. Here, we systematically measured messenger RNA (mRNA) dynamics across diverse breast cancer models, revealing that mRNA stability substantially shapes gene expression variability. To decipher these dynamics, we developed GreyHound, an interpretable multimodal deep-learning framework integrating RNA sequence features and RNA binding protein (RBP) expression. GreyHound identified an extensive network of RBPs and their regulons underlying variations in mRNA stability, including a regulatory axis centered on RBP RBMS3 and redox regulator TXNIP.\n                    <jats:italic toggle=\"yes\">RBMS3<\/jats:italic>\n                    depletion resulted in targeted transcript destabilization\u2014associated with poor clinical outcomes and enhanced metastatic potential in xenograft models. In vivo epistasis studies confirmed that RBMS3-mediated regulation of\n                    <jats:italic toggle=\"yes\">TXNIP<\/jats:italic>\n                    mRNA stability drives this metastasis-suppressive program. These findings identify a key posttranscriptional mechanism in breast cancer and illustrate how interpretable models of RNA dynamics can uncover regulatory programs in disease.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea9061","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:59:43Z","timestamp":1773251983000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Integrative analysis of mRNA stability regulation uncovers a metastasis-suppressive program in breast cancer"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6546-2319","authenticated-orcid":true,"given":"Heather","family":"Karner","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA."},{"name":"Department of Urology, University of California San Francisco, San Francisco, San Francisco, CA, USA."},{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7567-6252","authenticated-orcid":true,"given":"Tabea C.","family":"Mittmann","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA."},{"name":"Department of Urology, University of California San Francisco, San Francisco, San Francisco, CA, USA."},{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA."},{"name":"Faculty of Medicine, University of M\u00fcnster, M\u00fcnster, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9420-4591","authenticated-orcid":true,"given":"Vicky W.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA."},{"name":"Department of Urology, University of California San Francisco, San Francisco, San Francisco, CA, USA."},{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA."},{"name":"Department of Genetics, Stanford University, Palo Alto, CA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashir A.","family":"Borah","sequence":"additional","affiliation":[{"name":"Department of Urology, University of California San Francisco, San Francisco, San Francisco, CA, USA."},{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA."},{"name":"Biological and Medical Informatics Graduate Program, University of California, San Francisco, San Francisco, CA, USA."},{"name":"Arc Institute, Palo Alto, CA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Langen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco CA, USA."},{"name":"Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5867-1531","authenticated-orcid":true,"given":"Hassan","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA."},{"name":"Department of Urology, University of California San Francisco, San Francisco, San Francisco, CA, USA."},{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, 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