Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs
MicroRNAs (miRNAs) regulate numerous biological processes by base-pairing with target messenger RNAs (mRNAs), primarily through sites in 3′ untranslated regions (UTRs), to direct the repression of these targets. Although miRNAs have sometimes been observed to target genes through sites in open readi...
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| Format: | Article |
| Language: | en_US |
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Cold Spring Harbor Laboratory Press
2013
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| Online Access: | http://hdl.handle.net/1721.1/76793 https://orcid.org/0000-0002-3872-2856 https://orcid.org/0000-0002-2724-7228 |
| _version_ | 1811084168823570432 |
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| author | Schnall-Levin, Michael Rissland, Olivia S. Johnston, Wendy K. Perrimon, Norbert Bartel, David Berger Leighton, Bonnie |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Schnall-Levin, Michael Rissland, Olivia S. Johnston, Wendy K. Perrimon, Norbert Bartel, David Berger Leighton, Bonnie |
| author_sort | Schnall-Levin, Michael |
| collection | MIT |
| description | MicroRNAs (miRNAs) regulate numerous biological processes by base-pairing with target messenger RNAs (mRNAs), primarily through sites in 3′ untranslated regions (UTRs), to direct the repression of these targets. Although miRNAs have sometimes been observed to target genes through sites in open reading frames (ORFs), large-scale studies have shown such targeting to be generally less effective than 3′ UTR targeting. Here, we show that several miRNAs each target significant groups of genes through multiple sites within their coding regions. This ORF targeting, which mediates both predictable and effective repression, arises from highly repeated sequences containing miRNA target sites. We show that such sequence repeats largely arise through evolutionary duplications and occur particularly frequently within families of paralogous C[subscript 2]H[subscript 2] zinc-finger genes, suggesting the potential for their coordinated regulation. Examples of ORFs targeted by miR-181 include both the well-known tumor suppressor RB1 and RBAK, encoding a C[subscript 2]H[subscript 2] zinc-finger protein and transcriptional binding partner of RB1. Our results indicate a function for repeat-rich coding sequences in mediating post-transcriptional regulation and reveal circumstances in which miRNA-mediated repression through ORF sites can be reliably predicted. |
| first_indexed | 2024-09-23T12:45:59Z |
| format | Article |
| id | mit-1721.1/76793 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:45:59Z |
| publishDate | 2013 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/767932022-09-28T09:55:57Z Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs Schnall-Levin, Michael Rissland, Olivia S. Johnston, Wendy K. Perrimon, Norbert Bartel, David Berger Leighton, Bonnie Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Mathematics Schnall-Levin, Michael Rissland, Olivia S. Johnston, Wendy K. Bartel, David Berger, Bonnie MicroRNAs (miRNAs) regulate numerous biological processes by base-pairing with target messenger RNAs (mRNAs), primarily through sites in 3′ untranslated regions (UTRs), to direct the repression of these targets. Although miRNAs have sometimes been observed to target genes through sites in open reading frames (ORFs), large-scale studies have shown such targeting to be generally less effective than 3′ UTR targeting. Here, we show that several miRNAs each target significant groups of genes through multiple sites within their coding regions. This ORF targeting, which mediates both predictable and effective repression, arises from highly repeated sequences containing miRNA target sites. We show that such sequence repeats largely arise through evolutionary duplications and occur particularly frequently within families of paralogous C[subscript 2]H[subscript 2] zinc-finger genes, suggesting the potential for their coordinated regulation. Examples of ORFs targeted by miR-181 include both the well-known tumor suppressor RB1 and RBAK, encoding a C[subscript 2]H[subscript 2] zinc-finger protein and transcriptional binding partner of RB1. Our results indicate a function for repeat-rich coding sequences in mediating post-transcriptional regulation and reveal circumstances in which miRNA-mediated repression through ORF sites can be reliably predicted. Howard Hughes Medical Institute (Investigator) National Institutes of Health (U.S.) (Grant GM067031) National Institutes of Health (U.S.) (Grant 1R01GM081871) Hertz Foundation American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship Ruth L. Kirschstein National Research Service (Award GM088872) 2013-02-13T15:51:14Z 2013-02-13T15:51:14Z 2011-06 2011-01 Article http://purl.org/eprint/type/JournalArticle 1088-9051 http://hdl.handle.net/1721.1/76793 Schnall-Levin, M. et al. “Unusually Effective microRNA Targeting Within Repeat-rich Coding Regions of Mammalian mRNAs.” Genome Research 21.9 (2011): 1395–1403. Copyright © 2011 by Cold Spring Harbor Laboratory Press https://orcid.org/0000-0002-3872-2856 https://orcid.org/0000-0002-2724-7228 en_US http://dx.doi.org/10.1101/gr.121210.111 Genome Research Creative Commons Attribution Non-Commercial http://creativecommons.org/licenses/by-nc/3.0 application/pdf Cold Spring Harbor Laboratory Press Genome Research |
| spellingShingle | Schnall-Levin, Michael Rissland, Olivia S. Johnston, Wendy K. Perrimon, Norbert Bartel, David Berger Leighton, Bonnie Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs |
| title | Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs |
| title_full | Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs |
| title_fullStr | Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs |
| title_full_unstemmed | Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs |
| title_short | Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs |
| title_sort | unusually effective microrna targeting within repeat rich coding regions of mammalian mrnas |
| url | http://hdl.handle.net/1721.1/76793 https://orcid.org/0000-0002-3872-2856 https://orcid.org/0000-0002-2724-7228 |
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