MapToCleave: High-throughput profiling of microRNA biogenesis in living cells

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• dc.contributor.author Kang, Wenjing
• dc.contributor.author Fromm, Bastian
• dc.contributor.author Houben, Anna J.
• dc.contributor.author Høye, Eirik
• dc.contributor.author Bezdan, Daniela
• dc.contributor.author Arnan Ros, Carme
• dc.contributor.author Thrane, Kim
• dc.contributor.author Asp, Michaela
• dc.contributor.author Johnson, Rory
• dc.contributor.author Biryukova, Inna
• dc.contributor.author Friedländer, Marc R.
• dc.date.accessioned 2022-03-08T10:27:38Z
• dc.date.available 2022-03-08T10:27:38Z
• dc.date.issued 2021
• dc.description.abstract Previous large-scale studies have uncovered many features that determine the processing of microRNA (miRNA) precursors; however, they have been conducted in vitro. Here, we introduce MapToCleave, a method to simultaneously profile processing of thousands of distinct RNA structures in living cells. We find that miRNA precursors with a stable lower basal stem are more efficiently processed and also have higher expression in vivo in tissues from 20 animal species. We systematically compare the importance of known and novel sequence and structural features and test biogenesis of miRNA precursors from 10 animal and plant species in human cells. Lastly, we provide evidence that the GHG motif better predicts processing when defined as a structure rather than sequence motif, consistent with recent cryogenic electron microscopy (cryo-EM) studies. In summary, we apply a screening assay in living cells to reveal the importance of lower basal stem stability for miRNA processing and in vivo expression.
• dc.description.sponsorship This work was supported by the following sources: ERC starting grant 758397, “miRCell”; Swedish Research Council (VR) grant 2015-04611, “MapToCleave”; and funding from the Strategic Research Area (SFO) program of the Swedish Research Council through Stockholm University. R.J. is supported by Science Foundation Ireland through Future Research Leaders award 18/FRL/6194. C.A. was supported by the Ministerio de Economía y Competitividad and FEDER funds under reference numbers BIO2011-26205 and BIO2015-70777-P and Secretaria d’Universitats i Investigació del Departament d’Economia i Coneixement de la Generalitat de Catalunya under award number 2014 SGR 1319. A.J.H. was funded as a Marie Curie Post-doctoral Fellow supported by the European Commission 7th Framework Program under grant agreement no. 330133. The computations were enabled by resources in a project (SNIC 2017/7-297) provided by the Swedish National Infrastructure for Computing (SNIC) at UPPMAX, partially funded by the Swedish Research Council through grant agreement no. 2018-05973
• dc.format.mimetype application/pdf
• dc.identifier.citation Kang W, Fromm B, Houben AJ, Høye E, Bezdan D, Arnan C et al. MapToCleave: High-throughput profiling of microRNA biogenesis in living cells. Cell Rep. 2021 Nov 16;37(7):110015. DOI: 10.1016/j.celrep.2021.110015
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2021.110015
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/52651
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/330133
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/758397
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/26205
• dc.rights © 2021. Wenjing Kang et al. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other RNA
• dc.subject.other Vida -- Origen
• dc.subject.other Genètica
• dc.title MapToCleave: High-throughput profiling of microRNA biogenesis in living cells
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion