Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics
MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as doubl...
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| Veröffentlicht in: | Molecular therapy 2016-05, Vol.24 (5), p.946-955 |
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| creator | Matsui, Masayuki Prakash, Thazha P Corey, David R |
| description | MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development. |
| doi_str_mv | 10.1038/mt.2016.39 |
| format | Article |
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Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1038/mt.2016.39</identifier><identifier>PMID: 26903376</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>A549 Cells ; Animals ; Argonaute Proteins - genetics ; Argonaute Proteins - metabolism ; Biochemistry ; Biomimetic Materials - chemical synthesis ; Biomimetic Materials - chemistry ; Biomimetic Materials - pharmacology ; Cell culture ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Silencing ; HeLa Cells ; Hep G2 Cells ; Humans ; MicroRNAs ; MicroRNAs - chemical synthesis ; MicroRNAs - genetics ; Molecular Mimicry ; Original ; Proteins</subject><ispartof>Molecular therapy, 2016-05, Vol.24 (5), p.946-955</ispartof><rights>2016 Official journal of the American Society of Gene & Cell Therapy</rights><rights>Copyright Nature Publishing Group May 2016</rights><rights>Copyright © 2016 Official journal of the American Society of Gene & Cell Therapy 2016 Official journal of the American Society of Gene & Cell Therapy</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-51be95a37a7adce347382697e5b8a3ca5f955de8c1af233dd78c2781d97ef1933</citedby><cites>FETCH-LOGICAL-c484t-51be95a37a7adce347382697e5b8a3ca5f955de8c1af233dd78c2781d97ef1933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881773/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881773/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26903376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsui, Masayuki</creatorcontrib><creatorcontrib>Prakash, Thazha P</creatorcontrib><creatorcontrib>Corey, David R</creatorcontrib><title>Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development.</description><subject>A549 Cells</subject><subject>Animals</subject><subject>Argonaute Proteins - genetics</subject><subject>Argonaute Proteins - metabolism</subject><subject>Biochemistry</subject><subject>Biomimetic Materials - chemical synthesis</subject><subject>Biomimetic Materials - chemistry</subject><subject>Biomimetic Materials - pharmacology</subject><subject>Cell culture</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Silencing</subject><subject>HeLa Cells</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>MicroRNAs</subject><subject>MicroRNAs - chemical synthesis</subject><subject>MicroRNAs - genetics</subject><subject>Molecular Mimicry</subject><subject>Original</subject><subject>Proteins</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkVFLHDEUhYO0VKt98QeUgb5IYdZkMpkkL4VF1ApWQdvnkE3ubCMzyZpkRP99s127aCn0KZfky-HccxA6JHhGMBXHY541mHQzKnfQHmENqzFu2jfbmXS76H1Kd2UiTHbv0G7TSUwp7_bQ7Twug9dThqqpLazAW_C5uoHlNOjsgq9CX52Dh-r0cRUhpfXV4qm6dX45QJ1y1OWHrUZ3czWvvrnRmXSA3vZ6SPDh-dxHP85Ov598rS-vzy9O5pe1aUWba0YWIJmmXHNtDdCWU1GMcWALoanRrJeMWRCG6L6h1FouTMMFsQXpiaR0H33Z6K6mxQhFwhc3g1pFN-r4pIJ26vWLdz_VMjyoVgjC-Vrg6FkghvsJUlajSwaGQXsIU1JEYNERQaX4P8olbjteAi_op7_QuzBFX5L4TeFivWsK9XlDmRhSitBvfROs1rWqMat1rYrKAn98uekW_dNjAdoNACXvBwdRJePAG7AugsnKBvcv3V85bK7u</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Matsui, Masayuki</creator><creator>Prakash, Thazha P</creator><creator>Corey, David R</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><general>Nature Publishing Group</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20160501</creationdate><title>Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics</title><author>Matsui, Masayuki ; 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| subjects | A549 Cells Animals Argonaute Proteins - genetics Argonaute Proteins - metabolism Biochemistry Biomimetic Materials - chemical synthesis Biomimetic Materials - chemistry Biomimetic Materials - pharmacology Cell culture Gene expression Gene Expression Regulation, Neoplastic - drug effects Gene Silencing HeLa Cells Hep G2 Cells Humans MicroRNAs MicroRNAs - chemical synthesis MicroRNAs - genetics Molecular Mimicry Original Proteins |
| title | Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics |
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