miRNA-like duplexes as RNAi triggers with improved specificity
siRNA duplexes, the most common triggers of RNA interference, are first loaded into an Argonaute (Ago) protein and then undergo unwinding via passenger strand cleavage, which requires the slicer activity of the Ago protein. In mammals, only Ago2 out of the four Ago proteins possesses such slicer act...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-07-01
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| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2012.00127/full |
| _version_ | 1828872300127059968 |
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| author | Juan G. Betancur Juan G. Betancur Mayuko eYoda Mayuko eYoda Yukihide eTomari Yukihide eTomari |
| author_facet | Juan G. Betancur Juan G. Betancur Mayuko eYoda Mayuko eYoda Yukihide eTomari Yukihide eTomari |
| author_sort | Juan G. Betancur |
| collection | DOAJ |
| description | siRNA duplexes, the most common triggers of RNA interference, are first loaded into an Argonaute (Ago) protein and then undergo unwinding via passenger strand cleavage, which requires the slicer activity of the Ago protein. In mammals, only Ago2 out of the four Ago proteins possesses such slicer activity. In contrast, miRNA/miRNA* duplexes often contain central mismatches that prevent slicer-dependent unwinding. Instead, mismatches in specific regions (seed and 3´-mid regions) promote efficient slicer-independent unwinding by any of the four mammalian Ago proteins. Both slicer-dependent and slicer-independent unwinding mechanisms produce guide-containing RNA-induced silencing complex (RISC), which silences target mRNAs by cleavage, translational repression, and/or deadenylation that leads to mRNA decay. In this review, we summarize our current knowledge of the RISC assembly pathways, and describe a simple method to rationally design artificial miRNA/miRNA*-like duplexes and highlight its benefits to reduce the unwanted off-target effects without compromising the specific target silencing activity. |
| first_indexed | 2024-12-13T06:51:07Z |
| format | Article |
| id | doaj.art-41ba3ab1b1834e239724d0928d5ac7ce |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-13T06:51:07Z |
| publishDate | 2012-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-41ba3ab1b1834e239724d0928d5ac7ce2022-12-21T23:56:09ZengFrontiers Media S.A.Frontiers in Genetics1664-80212012-07-01310.3389/fgene.2012.0012727400miRNA-like duplexes as RNAi triggers with improved specificityJuan G. Betancur0Juan G. Betancur1Mayuko eYoda2Mayuko eYoda3Yukihide eTomari4Yukihide eTomari5The University of TokyoThe University of TokyoThe University of TokyoThe University of TokyoThe University of TokyoThe University of TokyosiRNA duplexes, the most common triggers of RNA interference, are first loaded into an Argonaute (Ago) protein and then undergo unwinding via passenger strand cleavage, which requires the slicer activity of the Ago protein. In mammals, only Ago2 out of the four Ago proteins possesses such slicer activity. In contrast, miRNA/miRNA* duplexes often contain central mismatches that prevent slicer-dependent unwinding. Instead, mismatches in specific regions (seed and 3´-mid regions) promote efficient slicer-independent unwinding by any of the four mammalian Ago proteins. Both slicer-dependent and slicer-independent unwinding mechanisms produce guide-containing RNA-induced silencing complex (RISC), which silences target mRNAs by cleavage, translational repression, and/or deadenylation that leads to mRNA decay. In this review, we summarize our current knowledge of the RISC assembly pathways, and describe a simple method to rationally design artificial miRNA/miRNA*-like duplexes and highlight its benefits to reduce the unwanted off-target effects without compromising the specific target silencing activity.http://journal.frontiersin.org/Journal/10.3389/fgene.2012.00127/fullmiRNAsRNA silencingArgonauteRISCsiRNAs |
| spellingShingle | Juan G. Betancur Juan G. Betancur Mayuko eYoda Mayuko eYoda Yukihide eTomari Yukihide eTomari miRNA-like duplexes as RNAi triggers with improved specificity Frontiers in Genetics miRNAs RNA silencing Argonaute RISC siRNAs |
| title | miRNA-like duplexes as RNAi triggers with improved specificity |
| title_full | miRNA-like duplexes as RNAi triggers with improved specificity |
| title_fullStr | miRNA-like duplexes as RNAi triggers with improved specificity |
| title_full_unstemmed | miRNA-like duplexes as RNAi triggers with improved specificity |
| title_short | miRNA-like duplexes as RNAi triggers with improved specificity |
| title_sort | mirna like duplexes as rnai triggers with improved specificity |
| topic | miRNAs RNA silencing Argonaute RISC siRNAs |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2012.00127/full |
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