Dicer-independent processing of short hairpin RNAs

Dicer-independent processing of short hairpin RNAs

Short hairpin RNAs (shRNAs) are widely used to induce RNA interference (RNAi). We tested a variety of shRNAs that differed in stem length and terminal loop size and revealed strikingly different RNAi activities and shRNA-processing patterns. Interestingly, we identified a specific shRNA design that...

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Main Authors: Liu, Ying Poi, Schopman, Nick C. T., Berkhout, Ben
Format: Online
Language:English
Published: Oxford University Press 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616727/
id pubmed-3616727
recordtype oai_dc
spelling pubmed-36167272013-04-04 Dicer-independent processing of short hairpin RNAs Liu, Ying Poi Schopman, Nick C. T. Berkhout, Ben RNA Short hairpin RNAs (shRNAs) are widely used to induce RNA interference (RNAi). We tested a variety of shRNAs that differed in stem length and terminal loop size and revealed strikingly different RNAi activities and shRNA-processing patterns. Interestingly, we identified a specific shRNA design that uses an alternative Dicer-independent processing pathway. Detailed analyses indicated that a short shRNA stem length is critical for avoiding Dicer processing and activation of the alternative processing route, in which the shRNA is incorporated into RISC and processed by the AGO2-mediated slicer activity. Such alternatively processed shRNAs (AgoshRNAs) yield only a single RNA strand that effectively induces RNAi, whereas conventional shRNA processing results in an siRNA duplex of which both strands can trigger RNAi. Both the processing and subsequent RNAi activity of these AgoshRNAs are thus mediated by the RISC-component AGO2. These results have important implications for the future design of more specific RNAi therapeutics. Oxford University Press 2013-04 2013-02-01 /pmc/articles/PMC3616727/ /pubmed/23376931 http://dx.doi.org/10.1093/nar/gkt036 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Liu, Ying Poi
Schopman, Nick C. T.
Berkhout, Ben
spellingShingle Liu, Ying Poi
Schopman, Nick C. T.
Berkhout, Ben
Dicer-independent processing of short hairpin RNAs
author_facet Liu, Ying Poi
Schopman, Nick C. T.
Berkhout, Ben
author_sort Liu, Ying Poi
title Dicer-independent processing of short hairpin RNAs
title_short Dicer-independent processing of short hairpin RNAs
title_full Dicer-independent processing of short hairpin RNAs
title_fullStr Dicer-independent processing of short hairpin RNAs
title_full_unstemmed Dicer-independent processing of short hairpin RNAs
title_sort dicer-independent processing of short hairpin rnas
description Short hairpin RNAs (shRNAs) are widely used to induce RNA interference (RNAi). We tested a variety of shRNAs that differed in stem length and terminal loop size and revealed strikingly different RNAi activities and shRNA-processing patterns. Interestingly, we identified a specific shRNA design that uses an alternative Dicer-independent processing pathway. Detailed analyses indicated that a short shRNA stem length is critical for avoiding Dicer processing and activation of the alternative processing route, in which the shRNA is incorporated into RISC and processed by the AGO2-mediated slicer activity. Such alternatively processed shRNAs (AgoshRNAs) yield only a single RNA strand that effectively induces RNAi, whereas conventional shRNA processing results in an siRNA duplex of which both strands can trigger RNAi. Both the processing and subsequent RNAi activity of these AgoshRNAs are thus mediated by the RISC-component AGO2. These results have important implications for the future design of more specific RNAi therapeutics.
publisher Oxford University Press
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616727/
_version_ 1611967631515975680

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