Cargando…

Target Repression Induced by Endogenous microRNAs: Large Differences, Small Effects

MicroRNAs are small RNAs that regulate protein levels. It is commonly assumed that the expression level of a microRNA is directly correlated with its repressive activity – that is, highly expressed microRNAs will repress their target mRNAs more. Here we investigate the quantitative relationship betw...

Descripción completa

Detalles Bibliográficos
Autores principales: Kozomara, Ana, Hunt, Suzanne, Ninova, Maria, Griffiths-Jones, Sam, Ronshaugen, Matthew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139194/
https://www.ncbi.nlm.nih.gov/pubmed/25141277
http://dx.doi.org/10.1371/journal.pone.0104286
_version_ 1782331332228022272
author Kozomara, Ana
Hunt, Suzanne
Ninova, Maria
Griffiths-Jones, Sam
Ronshaugen, Matthew
author_facet Kozomara, Ana
Hunt, Suzanne
Ninova, Maria
Griffiths-Jones, Sam
Ronshaugen, Matthew
author_sort Kozomara, Ana
collection PubMed
description MicroRNAs are small RNAs that regulate protein levels. It is commonly assumed that the expression level of a microRNA is directly correlated with its repressive activity – that is, highly expressed microRNAs will repress their target mRNAs more. Here we investigate the quantitative relationship between endogenous microRNA expression and repression for 32 mature microRNAs in Drosophila melanogaster S2 cells. In general, we find that more abundant microRNAs repress their targets to a greater degree. However, the relationship between expression and repression is nonlinear, such that a 10-fold greater microRNA concentration produces only a 10% increase in target repression. The expression/repression relationship is the same for both dominant guide microRNAs and minor mature products (so-called passenger strands/microRNA* sequences). However, we find examples of microRNAs whose cellular concentrations differ by several orders of magnitude, yet induce similar repression of target mRNAs. Likewise, microRNAs with similar expression can have very different repressive abilities. We show that the association of microRNAs with Argonaute proteins does not explain this variation in repression. The observed relationship is consistent with the limiting step in target repression being the association of the microRNA/RISC complex with the target site. These findings argue that modest changes in cellular microRNA concentration will have minor effects on repression of targets.
format Online
Article
Text
id pubmed-4139194
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-41391942014-08-25 Target Repression Induced by Endogenous microRNAs: Large Differences, Small Effects Kozomara, Ana Hunt, Suzanne Ninova, Maria Griffiths-Jones, Sam Ronshaugen, Matthew PLoS One Research Article MicroRNAs are small RNAs that regulate protein levels. It is commonly assumed that the expression level of a microRNA is directly correlated with its repressive activity – that is, highly expressed microRNAs will repress their target mRNAs more. Here we investigate the quantitative relationship between endogenous microRNA expression and repression for 32 mature microRNAs in Drosophila melanogaster S2 cells. In general, we find that more abundant microRNAs repress their targets to a greater degree. However, the relationship between expression and repression is nonlinear, such that a 10-fold greater microRNA concentration produces only a 10% increase in target repression. The expression/repression relationship is the same for both dominant guide microRNAs and minor mature products (so-called passenger strands/microRNA* sequences). However, we find examples of microRNAs whose cellular concentrations differ by several orders of magnitude, yet induce similar repression of target mRNAs. Likewise, microRNAs with similar expression can have very different repressive abilities. We show that the association of microRNAs with Argonaute proteins does not explain this variation in repression. The observed relationship is consistent with the limiting step in target repression being the association of the microRNA/RISC complex with the target site. These findings argue that modest changes in cellular microRNA concentration will have minor effects on repression of targets. Public Library of Science 2014-08-20 /pmc/articles/PMC4139194/ /pubmed/25141277 http://dx.doi.org/10.1371/journal.pone.0104286 Text en © 2014 Kozomara et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kozomara, Ana
Hunt, Suzanne
Ninova, Maria
Griffiths-Jones, Sam
Ronshaugen, Matthew
Target Repression Induced by Endogenous microRNAs: Large Differences, Small Effects
title Target Repression Induced by Endogenous microRNAs: Large Differences, Small Effects
title_full Target Repression Induced by Endogenous microRNAs: Large Differences, Small Effects
title_fullStr Target Repression Induced by Endogenous microRNAs: Large Differences, Small Effects
title_full_unstemmed Target Repression Induced by Endogenous microRNAs: Large Differences, Small Effects
title_short Target Repression Induced by Endogenous microRNAs: Large Differences, Small Effects
title_sort target repression induced by endogenous micrornas: large differences, small effects
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139194/
https://www.ncbi.nlm.nih.gov/pubmed/25141277
http://dx.doi.org/10.1371/journal.pone.0104286
work_keys_str_mv AT kozomaraana targetrepressioninducedbyendogenousmicrornaslargedifferencessmalleffects
AT huntsuzanne targetrepressioninducedbyendogenousmicrornaslargedifferencessmalleffects
AT ninovamaria targetrepressioninducedbyendogenousmicrornaslargedifferencessmalleffects
AT griffithsjonessam targetrepressioninducedbyendogenousmicrornaslargedifferencessmalleffects
AT ronshaugenmatthew targetrepressioninducedbyendogenousmicrornaslargedifferencessmalleffects