{"corpus_id":2278846,"paper_sha":"8aeca9e5568020221be51dc14568a7e7dfd30005","doi":"10.1093/nar/gkq954","arxiv_id":null,"pmid":21149259,"pmcid":"3074164","mag_id":2112571151,"dblp_id":null,"acl_id":null,"title":"Design of small molecule-responsive microRNAs based on structural requirements for Drosha processing","year":2010,"publication_date":"2010-12-11","venue":"Nucleic Acids Research","journal":{"name":"Nucleic Acids Research","pages":"2981 - 2994","volume":"39"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't","Research Support, U.S. Gov't, Non-P.H.S."],"s2_fields_of_study":["Biology","Medicine","Chemistry"],"reference_count":56,"citation_count":93,"influential_citation_count":1,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Aptamers, Nucleotide","mj":false,"ui":"D052157"},{"d":"Base Sequence","mj":false,"ui":"D001483"},{"d":"HEK293 Cells","mj":false,"ui":"D057809"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Ligands","mj":false,"ui":"D008024"},{"d":"MicroRNAs","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D035683"},{"d":"Molecular Sequence Data","mj":false,"ui":"D008969"},{"d":"RNA Interference","mj":true,"ui":"D034622"},{"d":"Ribonuclease III","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D043244"}],"chemicals":[{"n":"Aptamers, Nucleotide","ui":"D052157","reg":"0"},{"n":"Ligands","ui":"D008024","reg":"0"},{"n":"MicroRNAs","ui":"D035683","reg":"0"},{"n":"Ribonuclease III","ui":"D043244","reg":"EC 3.1.26.3"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://academic.oup.com/nar/article-pdf/39/7/2981/16783386/gkq954.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/8aeca9e5568020221be51dc14568a7e7dfd30005","s2_open_access_license":"CCBYNC","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"MicroRNAs (miRNAs) are prevalent regulatory RNAs that mediate gene silencing and play key roles in diverse cellular processes. While synthetic RNA-based regulatory systems that integrate regulatory and sensing functions have been demonstrated, the lack of detail on miRNA structure–function relationships has limited the development of integrated control systems based on miRNA silencing. Using an elucidated relationship between Drosha processing and the single-stranded nature of the miRNA basal segments, we developed a strategy for designing ligand-responsive miRNAs. We demonstrate that ligand binding to an aptamer integrated into the miRNA basal segments inhibits Drosha processing, resulting in titratable control over gene silencing. The generality of this control strategy was shown for three aptamer–small molecule ligand pairs. The platform can be extended to the design of synthetic miRNAs clusters, cis-acting miRNAs and self-targeting miRNAs that act both in cis and trans, enabling fine-tuning of the regulatory strength and dynamics. 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