{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T12:26:05Z","timestamp":1787833565379,"version":"build-2784847793"},"posted":{"date-parts":[[2026,8,24]]},"group-title":"Cell Biology","reference-count":153,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"crossref","award":["RR210012"],"award-info":[{"award-number":["RR210012"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R00HG010910"],"award-info":[{"award-number":["R00HG010910"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R35HG011909"],"award-info":[{"award-number":["R35HG011909"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R35GM154922"],"award-info":[{"award-number":["1R35GM154922"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32GM150582"],"award-info":[{"award-number":["T32GM150582"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R35GM137819"],"award-info":[{"award-number":["1R35GM137819"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"crossref","award":["Q-2186-20240404"],"award-info":[{"award-number":["Q-2186-20240404"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Caroline Wiess Law Seed Fund"},{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant"},{"name":"NSERC Alliance International Catalyst Grant"},{"name":"Toronto Metropolitan University Faculty of Science Startup Funds"},{"name":"Toronto Metropolitan University Faculty of Science Dean\u2019s Research Fund Startup Funds"},{"name":"BCM Seed Funds"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Most biological processes are dynamic, yet experimental methods predominantly rely on steady-state measurements to investigate their underlying mechanisms. RNA localization is a fundamental aspect of eukaryotic cell organization and is dynamically regulated by cells. While extensively studied in specialized cell types for a limited number of candidate RNAs, the general principles governing dynamic RNA localization at a transcriptome-wide scale remain largely unexplored. Existing transcriptome-wide studies provide only a static snapshot of RNAs residing in specific cellular locales, in part due to the limited availability of tools for probing cellular spatial organization at biologically relevant scales.<\/jats:p>\n                <jats:p>Here, we leverage the high spatial (tens of nanometers) and temporal (minute) resolution of APEX-seq to quantitatively measure the dependence of RNA transport on molecular motors at a transcriptome-wide scale in living cells. We conducted these experiments in the context of the localization of mRNAs to the mitochondria, which are essential for cellular function. Our findings indicate that the majority of nuclear-encoded RNAs encoding mitochondrial proteins localize to the outer mitochondrial membrane (OMM) for local translation. We reveal a crucial role of retrograde dynein-based motor transport in RNA localization, demonstrating that its disruption severely impairs RNA targeting to the OMM.<\/jats:p>\n                <jats:p>Time-resolved profiling of RNAs at the OMM revealed that localization is an active process, and even a brief disruption of transport for a few minutes results in a dramatic loss of localization. Moreover, we demonstrate that the translation efficiency (TE) of localized RNAs is a critical determinant of RNA localization in the context of motor-driven transport, as RNAs that delocalize following motor-transport perturbations exhibit lower TE. Using our temporal perturbation data, we also developed a spatiotemporal model that utilizes translation kinetics to capture key features of RNA localization dynamics at the OMM. Together, experiments and modeling suggest that the process of local translation at the OMM is kinetically controlled by the cell, and reveal an unappreciated mechanism by which active transport of RNAs enables cells to modulate their translation within minutes through RNA localization control.<\/jats:p>\n                <jats:p>Our study demonstrates how simultaneously capturing the kinetics of hundreds of transcripts with minute resolution can uncover general principles of cellular and organelle organization. Together, these experiments and modeling reveal how active transport and translation jointly maintain the OMM-localized transcriptome. More broadly, they identify RNA localization to cellular membranes as a rapidly tunable mechanism for controlling local translation, even in non-polarized cells.<\/jats:p>","DOI":"10.64898\/2026.08.22.746448","type":"posted-content","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:43:52Z","timestamp":1787586232000},"source":"Crossref","is-referenced-by-count":0,"title":["Kinetic Control of Nuclear-encoded Mitochondrial mRNA Localization and Local Translation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4405-0339","authenticated-orcid":false,"given":"Surbhi","family":"Sharma","sequence":"first","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Therapeutic Innovation Center (THINC), Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Wang","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Therapeutic Innovation Center (THINC), Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Therapeutic Innovation Center (THINC), Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline E.","family":"Rasband","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Therapeutic Innovation Center (THINC), Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinh T.","family":"Tat","sequence":"additional","affiliation":[{"name":"Center for RNA Therapeutics, 6670 Bertner Ave, Houston, TX 77030 USA"},{"name":"Department of Cardiovascular Sciences, 6670 Bertner Ave, Houston, TX 77030 USA"},{"name":"Houston Methodist Academic Institute, 6670 Bertner Ave, Houston, TX 77030 USA"},{"name":"Houston Methodist Neal Cancer Center, 6670 Bertner Ave, Houston, TX 77030 USA"},{"name":"Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabha","family":"Chupal","sequence":"additional","affiliation":[{"name":"Department of Physics, Toronto Metropolitan University, Toronto M5B 2K3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Yun","family":"Chang","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Therapeutic Innovation Center (THINC), Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L.","family":"Van Nostrand","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Therapeutic Innovation Center (THINC), Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Kiss","sequence":"additional","affiliation":[{"name":"Center for RNA Therapeutics, 6670 Bertner Ave, Houston, TX 77030 USA"},{"name":"Department of Cardiovascular Sciences, 6670 Bertner Ave, Houston, TX 77030 USA"},{"name":"Houston Methodist Academic Institute, 6670 Bertner Ave, Houston, TX 77030 USA"},{"name":"Center for Bionanoengineering, 6670 Bertner Ave, Houston, TX 77030 USA"},{"name":"Houston Methodist Neal Cancer Center, 6670 Bertner Ave, Houston, TX 77030 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan I.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Physics, Toronto Metropolitan University, Toronto M5B 2K3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0758-4582","authenticated-orcid":false,"given":"Furqan M.","family":"Fazal","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Therapeutic Innovation Center (THINC), Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Dan L. 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