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Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs

Most metazoan microRNAs (miRNAs) target many genes for repression, but the nematode lsy-6 miRNA is much less proficient. Here, we show that the low proficiency of lsy-6 can be recapitulated in HeLa cells and that miR-23 (a mammalian miRNA) also has low proficiency in these cells. Reporter results an...

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Autores principales: Garcia, David M., Baek, Daehyun, Shin, Chanseok, Bell, George W., Grimson, Andrew, Bartel, David P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190056/
https://www.ncbi.nlm.nih.gov/pubmed/21909094
http://dx.doi.org/10.1038/nsmb.2115
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author Garcia, David M.
Baek, Daehyun
Shin, Chanseok
Bell, George W.
Grimson, Andrew
Bartel, David P.
author_facet Garcia, David M.
Baek, Daehyun
Shin, Chanseok
Bell, George W.
Grimson, Andrew
Bartel, David P.
author_sort Garcia, David M.
collection PubMed
description Most metazoan microRNAs (miRNAs) target many genes for repression, but the nematode lsy-6 miRNA is much less proficient. Here, we show that the low proficiency of lsy-6 can be recapitulated in HeLa cells and that miR-23 (a mammalian miRNA) also has low proficiency in these cells. Reporter results and array data both indicate two properties of these miRNAs that impart low proficiency: their weak predicted seed-pairing stability (SPS) and their high target-site abundance (TA). These two properties also explain differential propensities of small interfering RNAs (siRNAs) to repress unintended targets. Using these insights, we expand the TargetScan tool for quantitatively predicting miRNA regulation (and siRNA off-targeting) so as to model differential miRNA (siRNA) proficiencies, thereby improving prediction performance. Moreover, we propose that siRNAs designed to have both weaker SPS and higher TA will have fewer off-targets without compromised on-target activity.
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spelling pubmed-31900562012-04-01 Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs Garcia, David M. Baek, Daehyun Shin, Chanseok Bell, George W. Grimson, Andrew Bartel, David P. Nat Struct Mol Biol Article Most metazoan microRNAs (miRNAs) target many genes for repression, but the nematode lsy-6 miRNA is much less proficient. Here, we show that the low proficiency of lsy-6 can be recapitulated in HeLa cells and that miR-23 (a mammalian miRNA) also has low proficiency in these cells. Reporter results and array data both indicate two properties of these miRNAs that impart low proficiency: their weak predicted seed-pairing stability (SPS) and their high target-site abundance (TA). These two properties also explain differential propensities of small interfering RNAs (siRNAs) to repress unintended targets. Using these insights, we expand the TargetScan tool for quantitatively predicting miRNA regulation (and siRNA off-targeting) so as to model differential miRNA (siRNA) proficiencies, thereby improving prediction performance. Moreover, we propose that siRNAs designed to have both weaker SPS and higher TA will have fewer off-targets without compromised on-target activity. 2011-09-11 /pmc/articles/PMC3190056/ /pubmed/21909094 http://dx.doi.org/10.1038/nsmb.2115 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Garcia, David M.
Baek, Daehyun
Shin, Chanseok
Bell, George W.
Grimson, Andrew
Bartel, David P.
Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs
title Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs
title_full Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs
title_fullStr Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs
title_full_unstemmed Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs
title_short Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs
title_sort weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other mirnas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190056/
https://www.ncbi.nlm.nih.gov/pubmed/21909094
http://dx.doi.org/10.1038/nsmb.2115
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