Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing.
microRNAs (miRNAs) silence gene expression by suppressing protein production and/or by promoting mRNA decay. To elucidate how silencing is accomplished, we screened an RNA interference library for suppressors of miRNA-mediated regulation in Drosophila melanogaster cells. In addition to proteins know...
| Hoofdauteurs: | , , , , , , , , , |
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| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
2007
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| _version_ | 1826277214105108480 |
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| author | Eulalio, A Rehwinkel, J Stricker, M Huntzinger, E Yang, S Doerks, T Dorner, S Bork, P Boutros, M Izaurralde, E |
| author_facet | Eulalio, A Rehwinkel, J Stricker, M Huntzinger, E Yang, S Doerks, T Dorner, S Bork, P Boutros, M Izaurralde, E |
| author_sort | Eulalio, A |
| collection | OXFORD |
| description | microRNAs (miRNAs) silence gene expression by suppressing protein production and/or by promoting mRNA decay. To elucidate how silencing is accomplished, we screened an RNA interference library for suppressors of miRNA-mediated regulation in Drosophila melanogaster cells. In addition to proteins known to be required for miRNA biogenesis and function (i.e., Drosha, Pasha, Dicer-1, AGO1, and GW182), the screen identified the decapping activator Ge-1 as being required for silencing by miRNAs. Depleting Ge-1 alone and/or in combination with other decapping activators (e.g., DCP1, EDC3, HPat, or Me31B) suppresses silencing of several miRNA targets, indicating that miRNAs elicit mRNA decapping. A comparison of gene expression profiles in cells depleted of AGO1 or of individual decapping activators shows that approximately 15% of AGO1-targets are also regulated by Ge-1, DCP1, and HPat, whereas 5% are dependent on EDC3 and LSm1-7. These percentages are underestimated because decapping activators are partially redundant. Furthermore, in the absence of active translation, some miRNA targets are stabilized, whereas others continue to be degraded in a miRNA-dependent manner. These findings suggest that miRNAs mediate post-transcriptional gene silencing by more than one mechanism. |
| first_indexed | 2024-03-06T23:25:32Z |
| format | Journal article |
| id | oxford-uuid:6a3e9f3a-df7a-4293-abfd-e944d5f948b0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:25:32Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:6a3e9f3a-df7a-4293-abfd-e944d5f948b02022-03-26T18:56:09ZTarget-specific requirements for enhancers of decapping in miRNA-mediated gene silencing.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6a3e9f3a-df7a-4293-abfd-e944d5f948b0EnglishSymplectic Elements at Oxford2007Eulalio, ARehwinkel, JStricker, MHuntzinger, EYang, SDoerks, TDorner, SBork, PBoutros, MIzaurralde, EmicroRNAs (miRNAs) silence gene expression by suppressing protein production and/or by promoting mRNA decay. To elucidate how silencing is accomplished, we screened an RNA interference library for suppressors of miRNA-mediated regulation in Drosophila melanogaster cells. In addition to proteins known to be required for miRNA biogenesis and function (i.e., Drosha, Pasha, Dicer-1, AGO1, and GW182), the screen identified the decapping activator Ge-1 as being required for silencing by miRNAs. Depleting Ge-1 alone and/or in combination with other decapping activators (e.g., DCP1, EDC3, HPat, or Me31B) suppresses silencing of several miRNA targets, indicating that miRNAs elicit mRNA decapping. A comparison of gene expression profiles in cells depleted of AGO1 or of individual decapping activators shows that approximately 15% of AGO1-targets are also regulated by Ge-1, DCP1, and HPat, whereas 5% are dependent on EDC3 and LSm1-7. These percentages are underestimated because decapping activators are partially redundant. Furthermore, in the absence of active translation, some miRNA targets are stabilized, whereas others continue to be degraded in a miRNA-dependent manner. These findings suggest that miRNAs mediate post-transcriptional gene silencing by more than one mechanism. |
| spellingShingle | Eulalio, A Rehwinkel, J Stricker, M Huntzinger, E Yang, S Doerks, T Dorner, S Bork, P Boutros, M Izaurralde, E Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing. |
| title | Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing. |
| title_full | Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing. |
| title_fullStr | Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing. |
| title_full_unstemmed | Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing. |
| title_short | Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing. |
| title_sort | target specific requirements for enhancers of decapping in mirna mediated gene silencing |
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