Most mammalian mRNAs are conserved targets of microRNAs
MicroRNAs (miRNAs) are small endogenous RNAs that pair to sites in mRNAs to direct post-transcriptional repression. Many sites that match the miRNA seed (nucleotides 2–7), particularly those in 3′ untranslated regions (3′UTRs), are preferentially conserved. Here, we overhauled our tool for finding p...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Cold Spring Harbor Laboratory Press in association with The Genetics Society
2011
|
| Online Access: | http://hdl.handle.net/1721.1/65151 https://orcid.org/0000-0002-3872-2856 |
| _version_ | 1826192842543857664 |
|---|---|
| author | Friedman, Robin Carl Farh, Kyle Kai-How Bartel, David Burge, Christopher B |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Friedman, Robin Carl Farh, Kyle Kai-How Bartel, David Burge, Christopher B |
| author_sort | Friedman, Robin Carl |
| collection | MIT |
| description | MicroRNAs (miRNAs) are small endogenous RNAs that pair to sites in mRNAs to direct post-transcriptional repression. Many sites that match the miRNA seed (nucleotides 2–7), particularly those in 3′ untranslated regions (3′UTRs), are preferentially conserved. Here, we overhauled our tool for finding preferential conservation of sequence motifs and applied it to the analysis of human 3′UTRs, increasing by nearly threefold the detected number of preferentially conserved miRNA target sites. The new tool more efficiently incorporates new genomes and more completely controls for background conservation by accounting for mutational biases, dinucleotide conservation rates, and the conservation rates of individual UTRs. The improved background model enabled preferential conservation of a new site type, the “offset 6mer,” to be detected. In total, >45,000 miRNA target sites within human 3′UTRs are conserved above background levels, and >60% of human protein-coding genes have been under selective pressure to maintain pairing to miRNAs. Mammalian-specific miRNAs have far fewer conserved targets than do the more broadly conserved miRNAs, even when considering only more recently emerged targets. Although pairing to the 3′ end of miRNAs can compensate for seed mismatches, this class of sites constitutes less than 2% of all preferentially conserved sites detected. The new tool enables statistically powerful analysis of individual miRNA target sites, with the probability of preferentially conserved targeting (PCT) correlating with experimental measurements of repression. Our expanded set of target predictions (including conserved 3′-compensatory sites), are available at the TargetScan website, which displays the PCT for each site and each predicted target. |
| first_indexed | 2024-09-23T09:30:03Z |
| format | Article |
| id | mit-1721.1/65151 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:30:03Z |
| publishDate | 2011 |
| publisher | Cold Spring Harbor Laboratory Press in association with The Genetics Society |
| record_format | dspace |
| spelling | mit-1721.1/651512022-09-30T14:48:48Z Most mammalian mRNAs are conserved targets of microRNAs Friedman, Robin Carl Farh, Kyle Kai-How Bartel, David Burge, Christopher B Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Bartel, David Friedman, Robin Carl Farh, Kyle Kai-How Burge, Christopher B. Bartel, David MicroRNAs (miRNAs) are small endogenous RNAs that pair to sites in mRNAs to direct post-transcriptional repression. Many sites that match the miRNA seed (nucleotides 2–7), particularly those in 3′ untranslated regions (3′UTRs), are preferentially conserved. Here, we overhauled our tool for finding preferential conservation of sequence motifs and applied it to the analysis of human 3′UTRs, increasing by nearly threefold the detected number of preferentially conserved miRNA target sites. The new tool more efficiently incorporates new genomes and more completely controls for background conservation by accounting for mutational biases, dinucleotide conservation rates, and the conservation rates of individual UTRs. The improved background model enabled preferential conservation of a new site type, the “offset 6mer,” to be detected. In total, >45,000 miRNA target sites within human 3′UTRs are conserved above background levels, and >60% of human protein-coding genes have been under selective pressure to maintain pairing to miRNAs. Mammalian-specific miRNAs have far fewer conserved targets than do the more broadly conserved miRNAs, even when considering only more recently emerged targets. Although pairing to the 3′ end of miRNAs can compensate for seed mismatches, this class of sites constitutes less than 2% of all preferentially conserved sites detected. The new tool enables statistically powerful analysis of individual miRNA target sites, with the probability of preferentially conserved targeting (PCT) correlating with experimental measurements of repression. Our expanded set of target predictions (including conserved 3′-compensatory sites), are available at the TargetScan website, which displays the PCT for each site and each predicted target. National Institutes of Health (U.S.) Krell Institute United States. Dept. of Energy (Computational Sciences Graduate Fellowship) 2011-08-15T18:41:36Z 2011-08-15T18:41:36Z 2008-10 2008-10 Article http://purl.org/eprint/type/JournalArticle 1088-9051 1549-5469 http://hdl.handle.net/1721.1/65151 Friedman, R. C. et al. “Most Mammalian mRNAs Are Conserved Targets of microRNAs.” Genome Research 19.1 (2008) : 92-105.© 2009 Cold Spring Harbor Laboratory Press. https://orcid.org/0000-0002-3872-2856 en_US http://dx.doi.org/10.1101/gr.082701.108 Genome Research Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Cold Spring Harbor Laboratory Press in association with The Genetics Society Cold Spring Harbor Laboratory Press |
| spellingShingle | Friedman, Robin Carl Farh, Kyle Kai-How Bartel, David Burge, Christopher B Most mammalian mRNAs are conserved targets of microRNAs |
| title | Most mammalian mRNAs are conserved targets of microRNAs |
| title_full | Most mammalian mRNAs are conserved targets of microRNAs |
| title_fullStr | Most mammalian mRNAs are conserved targets of microRNAs |
| title_full_unstemmed | Most mammalian mRNAs are conserved targets of microRNAs |
| title_short | Most mammalian mRNAs are conserved targets of microRNAs |
| title_sort | most mammalian mrnas are conserved targets of micrornas |
| url | http://hdl.handle.net/1721.1/65151 https://orcid.org/0000-0002-3872-2856 |
| work_keys_str_mv | AT friedmanrobincarl mostmammalianmrnasareconservedtargetsofmicrornas AT farhkylekaihow mostmammalianmrnasareconservedtargetsofmicrornas AT barteldavid mostmammalianmrnasareconservedtargetsofmicrornas AT burgechristopherb mostmammalianmrnasareconservedtargetsofmicrornas |