The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs
Animal miRNAs are a large class of small regulatory RNAs that are known to directly and negatively regulate the expression of a large fraction of all protein encoding genes. The identification and characterization of miRNA targets is thus a fundamental problem in biology. miRNAs regulate target gene...
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Public Library of Science
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062573/ |
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pubmed-30625732011-03-28 The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs Fang, Zhuo Rajewsky, Nikolaus Research Article Animal miRNAs are a large class of small regulatory RNAs that are known to directly and negatively regulate the expression of a large fraction of all protein encoding genes. The identification and characterization of miRNA targets is thus a fundamental problem in biology. miRNAs regulate target genes by binding to 3′ untranslated regions (3′UTRs) of target mRNAs, and multiple binding sites for the same miRNA in 3′UTRs can strongly enhance the degree of regulation. Recent experiments have demonstrated that a large fraction of miRNA binding sites reside in coding sequences. Overall, miRNA binding sites in coding regions were shown to mediate smaller regulation than 3′UTR binding. However, possible interactions between target sites in coding sequences and 3′UTRs have not been studied. Using transcriptomics and proteomics data of ten miRNA mis-expression experiments as well as transcriptome-wide experimentally identified miRNA target sites, we found that mRNA and protein expression of genes containing target sites both in coding regions and 3′UTRs were in general mildly but significantly more regulated than those containing target sites in 3′UTRs only. These effects were stronger for conserved target sites of length 7–8 nt in coding regions compared to non-conserved sites. Combined with our other finding that miRNA target sites in coding regions are under negative selection, our results shed light on the functional importance of miRNA targeting in coding regions. Public Library of Science 2011-03-22 /pmc/articles/PMC3062573/ /pubmed/21445367 http://dx.doi.org/10.1371/journal.pone.0018067 Text en Fang, Rajewsky. 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. |
| 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 |
Fang, Zhuo Rajewsky, Nikolaus |
| spellingShingle |
Fang, Zhuo Rajewsky, Nikolaus The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs |
| author_facet |
Fang, Zhuo Rajewsky, Nikolaus |
| author_sort |
Fang, Zhuo |
| title |
The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs |
| title_short |
The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs |
| title_full |
The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs |
| title_fullStr |
The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs |
| title_full_unstemmed |
The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs |
| title_sort |
impact of mirna target sites in coding sequences and in 3′utrs |
| description |
Animal miRNAs are a large class of small regulatory RNAs that are known to directly and negatively regulate the expression of a large fraction of all protein encoding genes. The identification and characterization of miRNA targets is thus a fundamental problem in biology. miRNAs regulate target genes by binding to 3′ untranslated regions (3′UTRs) of target mRNAs, and multiple binding sites for the same miRNA in 3′UTRs can strongly enhance the degree of regulation. Recent experiments have demonstrated that a large fraction of miRNA binding sites reside in coding sequences. Overall, miRNA binding sites in coding regions were shown to mediate smaller regulation than 3′UTR binding. However, possible interactions between target sites in coding sequences and 3′UTRs have not been studied. Using transcriptomics and proteomics data of ten miRNA mis-expression experiments as well as transcriptome-wide experimentally identified miRNA target sites, we found that mRNA and protein expression of genes containing target sites both in coding regions and 3′UTRs were in general mildly but significantly more regulated than those containing target sites in 3′UTRs only. These effects were stronger for conserved target sites of length 7–8 nt in coding regions compared to non-conserved sites. Combined with our other finding that miRNA target sites in coding regions are under negative selection, our results shed light on the functional importance of miRNA targeting in coding regions. |
| publisher |
Public Library of Science |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062573/ |
| _version_ |
1611446607648129024 |