Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition
Target competition (ceRNA crosstalk) within miRNA-regulated gene networks has been proposed to influence biological systems. To assess target competition, we characterize and quantitate miRNA networks in two cell types. Argonaute iCLIP reveals that hierarchical binding of high- to low-affinity miRNA...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/106343 https://orcid.org/0000-0003-1465-1691 |
| _version_ | 1826213600747847680 |
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| author | Bosson, Andrew David Zamudio, Jesse Ray Sharp, Phillip A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Bosson, Andrew David Zamudio, Jesse Ray Sharp, Phillip A. |
| author_sort | Bosson, Andrew David |
| collection | MIT |
| description | Target competition (ceRNA crosstalk) within miRNA-regulated gene networks has been proposed to influence biological systems. To assess target competition, we characterize and quantitate miRNA networks in two cell types. Argonaute iCLIP reveals that hierarchical binding of high- to low-affinity miRNA targets is a key characteristic of in vivo activity. Quantification of cellular miRNA and mRNA/ncRNA target pool levels indicates that miRNA:target pool ratios and an affinity partitioned target pool accurately predict in vivo Ago binding profiles and miRNA susceptibility to target competition. Using single-cell reporters, we directly test predictions and estimate that ∼3,000 additional high-affinity target sites can affect active miRNA families with low endogenous miRNA:target ratios, such as miR-92/25. In contrast, the highly expressed miR-294 and let-7 families are not susceptible to increases of nearly 10,000 sites. These results show differential susceptibility based on endogenous miRNA:target pool ratios and provide a physiological context for ceRNA competition in vivo. |
| first_indexed | 2024-09-23T15:51:50Z |
| format | Article |
| id | mit-1721.1/106343 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:51:50Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1063432022-09-29T16:40:39Z Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition Bosson, Andrew David Zamudio, Jesse Ray Sharp, Phillip A. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Bosson, Andrew David Zamudio, Jesse Ray Sharp, Phillip A. Target competition (ceRNA crosstalk) within miRNA-regulated gene networks has been proposed to influence biological systems. To assess target competition, we characterize and quantitate miRNA networks in two cell types. Argonaute iCLIP reveals that hierarchical binding of high- to low-affinity miRNA targets is a key characteristic of in vivo activity. Quantification of cellular miRNA and mRNA/ncRNA target pool levels indicates that miRNA:target pool ratios and an affinity partitioned target pool accurately predict in vivo Ago binding profiles and miRNA susceptibility to target competition. Using single-cell reporters, we directly test predictions and estimate that ∼3,000 additional high-affinity target sites can affect active miRNA families with low endogenous miRNA:target ratios, such as miR-92/25. In contrast, the highly expressed miR-294 and let-7 families are not susceptible to increases of nearly 10,000 sites. These results show differential susceptibility based on endogenous miRNA:target pool ratios and provide a physiological context for ceRNA competition in vivo. National Institutes of Health (U.S.) (Grants RO1-GM34277 and R01-CA133404) National Cancer Institute (U.S.) (Grants PO1-CA42063 and F32CA139902) National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051) 2017-01-11T18:59:47Z 2017-01-11T18:59:47Z 2014-03 Article http://purl.org/eprint/type/JournalArticle 1097-2765 1097-4164 http://hdl.handle.net/1721.1/106343 Bosson, Andrew D., Jesse R. Zamudio, and Phillip A. Sharp. “Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition.” Molecular Cell 56.3 (2014): 347–359. https://orcid.org/0000-0003-1465-1691 en_US http://dx.doi.org/10.1016/j.molcel.2014.09.018 Molecular Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Bosson, Andrew David Zamudio, Jesse Ray Sharp, Phillip A. Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition |
| title | Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition |
| title_full | Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition |
| title_fullStr | Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition |
| title_full_unstemmed | Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition |
| title_short | Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition |
| title_sort | endogenous mirna and target concentrations determine susceptibility to potential cerna competition |
| url | http://hdl.handle.net/1721.1/106343 https://orcid.org/0000-0003-1465-1691 |
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