Mammalian miRNA RISC Recruits CAF1 and PABP to Affect PABP-Dependent Deadenylation
MicroRNAs (miRNAs) inhibit mRNA expression in general by base pairing to the 3′UTR of target mRNAs and consequently inhibiting translation and/or initiating poly(A) tail deadenylation and mRNA destabilization. Here we examine the mechanism and kinetics of miRNA-mediated deadenylation in mouse Krebs-...
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| Veröffentlicht in: | Molecular cell 2009-09, Vol.35 (6), p.868-880 |
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| creator | Fabian, Marc R. Mathonnet, Géraldine Sundermeier, Thomas Mathys, Hansruedi Zipprich, Jakob T. Svitkin, Yuri V. Rivas, Fabiola Jinek, Martin Wohlschlegel, James Doudna, Jennifer A. Chen, Chyi-Ying A. Shyu, Ann-Bin Yates, John R. Hannon, Gregory J. Filipowicz, Witold Duchaine, Thomas F. Sonenberg, Nahum |
| description | MicroRNAs (miRNAs) inhibit mRNA expression in general by base pairing to the 3′UTR of target mRNAs and consequently inhibiting translation and/or initiating poly(A) tail deadenylation and mRNA destabilization. Here we examine the mechanism and kinetics of miRNA-mediated deadenylation in mouse Krebs-2 ascites extract. We demonstrate that miRNA-mediated mRNA deadenylation occurs subsequent to initial translational inhibition, indicating a two-step mechanism of miRNA action, which serves to consolidate repression. We show that a let-7 miRNA-loaded RNA-induced silencing complex (miRISC) interacts with the poly(A)-binding protein (PABP) and the CAF1 and CCR4 deadenylases. In addition, we demonstrate that miRNA-mediated deadenylation is dependent upon CAF1 activity and PABP, which serves as a bona fide miRNA coactivator. Importantly, we present evidence that GW182, a core component of the miRISC, directly interacts with PABP via its C-terminal region and that this interaction is required for miRNA-mediated deadenylation. |
| doi_str_mv | 10.1016/j.molcel.2009.08.004 |
| format | Article |
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Here we examine the mechanism and kinetics of miRNA-mediated deadenylation in mouse Krebs-2 ascites extract. We demonstrate that miRNA-mediated mRNA deadenylation occurs subsequent to initial translational inhibition, indicating a two-step mechanism of miRNA action, which serves to consolidate repression. We show that a let-7 miRNA-loaded RNA-induced silencing complex (miRISC) interacts with the poly(A)-binding protein (PABP) and the CAF1 and CCR4 deadenylases. In addition, we demonstrate that miRNA-mediated deadenylation is dependent upon CAF1 activity and PABP, which serves as a bona fide miRNA coactivator. Importantly, we present evidence that GW182, a core component of the miRISC, directly interacts with PABP via its C-terminal region and that this interaction is required for miRNA-mediated deadenylation.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2009.08.004</identifier><identifier>PMID: 19716330</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Argonaute Proteins ; Ascites - genetics ; Ascites - metabolism ; Autoantigens - metabolism ; Binding Sites ; Carcinoma, Krebs 2 - genetics ; Carcinoma, Krebs 2 - metabolism ; Cell-Free System ; Eukaryotic Initiation Factor-2 - metabolism ; Eukaryotic Initiation Factor-4G - metabolism ; Gene Silencing ; HeLa Cells ; Humans ; Kinetics ; Mice ; MicroRNAs - metabolism ; Poly(A)-Binding Proteins - genetics ; Poly(A)-Binding Proteins - metabolism ; Protein Biosynthesis ; Protein Structure, Tertiary ; PROTEINS ; Proteins - genetics ; Proteins - metabolism ; Receptors, CCR4 - metabolism ; RNA ; RNA Processing, Post-Transcriptional ; RNA Stability ; RNA, Messenger - metabolism ; RNA-Induced Silencing Complex - genetics ; RNA-Induced Silencing Complex - metabolism ; Transfection</subject><ispartof>Molecular cell, 2009-09, Vol.35 (6), p.868-880</ispartof><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-618c2e9c134b7c77511c628c6f079209ea1932081d596b3846e12363fa88c1e33</citedby><cites>FETCH-LOGICAL-c527t-618c2e9c134b7c77511c628c6f079209ea1932081d596b3846e12363fa88c1e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1097276509005504$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19716330$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fabian, Marc R.</creatorcontrib><creatorcontrib>Mathonnet, Géraldine</creatorcontrib><creatorcontrib>Sundermeier, Thomas</creatorcontrib><creatorcontrib>Mathys, Hansruedi</creatorcontrib><creatorcontrib>Zipprich, Jakob T.</creatorcontrib><creatorcontrib>Svitkin, Yuri V.</creatorcontrib><creatorcontrib>Rivas, Fabiola</creatorcontrib><creatorcontrib>Jinek, Martin</creatorcontrib><creatorcontrib>Wohlschlegel, James</creatorcontrib><creatorcontrib>Doudna, Jennifer A.</creatorcontrib><creatorcontrib>Chen, Chyi-Ying A.</creatorcontrib><creatorcontrib>Shyu, Ann-Bin</creatorcontrib><creatorcontrib>Yates, John R.</creatorcontrib><creatorcontrib>Hannon, Gregory J.</creatorcontrib><creatorcontrib>Filipowicz, Witold</creatorcontrib><creatorcontrib>Duchaine, Thomas F.</creatorcontrib><creatorcontrib>Sonenberg, Nahum</creatorcontrib><title>Mammalian miRNA RISC Recruits CAF1 and PABP to Affect PABP-Dependent Deadenylation</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>MicroRNAs (miRNAs) inhibit mRNA expression in general by base pairing to the 3′UTR of target mRNAs and consequently inhibiting translation and/or initiating poly(A) tail deadenylation and mRNA destabilization. Here we examine the mechanism and kinetics of miRNA-mediated deadenylation in mouse Krebs-2 ascites extract. We demonstrate that miRNA-mediated mRNA deadenylation occurs subsequent to initial translational inhibition, indicating a two-step mechanism of miRNA action, which serves to consolidate repression. We show that a let-7 miRNA-loaded RNA-induced silencing complex (miRISC) interacts with the poly(A)-binding protein (PABP) and the CAF1 and CCR4 deadenylases. In addition, we demonstrate that miRNA-mediated deadenylation is dependent upon CAF1 activity and PABP, which serves as a bona fide miRNA coactivator. Importantly, we present evidence that GW182, a core component of the miRISC, directly interacts with PABP via its C-terminal region and that this interaction is required for miRNA-mediated deadenylation.</description><subject>Animals</subject><subject>Argonaute Proteins</subject><subject>Ascites - genetics</subject><subject>Ascites - metabolism</subject><subject>Autoantigens - metabolism</subject><subject>Binding Sites</subject><subject>Carcinoma, Krebs 2 - genetics</subject><subject>Carcinoma, Krebs 2 - metabolism</subject><subject>Cell-Free System</subject><subject>Eukaryotic Initiation Factor-2 - metabolism</subject><subject>Eukaryotic Initiation Factor-4G - metabolism</subject><subject>Gene Silencing</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Mice</subject><subject>MicroRNAs - metabolism</subject><subject>Poly(A)-Binding Proteins - genetics</subject><subject>Poly(A)-Binding Proteins - metabolism</subject><subject>Protein Biosynthesis</subject><subject>Protein Structure, Tertiary</subject><subject>PROTEINS</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Receptors, CCR4 - metabolism</subject><subject>RNA</subject><subject>RNA Processing, Post-Transcriptional</subject><subject>RNA Stability</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA-Induced Silencing Complex - genetics</subject><subject>RNA-Induced Silencing Complex - metabolism</subject><subject>Transfection</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAQtRCIlsI_QMgnbgljO_HHBSlsKVQqUC1wtrzOBLxK4q2drdR_j8uuKFw4zYxm5r2Z9wh5yaBmwOSbbT3F0eNYcwBTg64BmkfklIFRVcNk8_iYcyXbE_Is5y0Aa1ptnpITZhSTQsApWX9y0-TG4GY6hfXnjq4vv67oGn3ahyXTVXfBqJt7et29u6ZLpN0woF9-l9U57nDucV7oOboS70a3hDg_J08GN2Z8cYxn5PvF-2-rj9XVlw-Xq-6q8i1XSyWZ9hyNZ6LZKK9Uy5iXXHs5gDIcDDpmBAfN-tbIjdCNRMaFFIPT2jMU4oy8PeDu9psJe18OSW60uxQml-5sdMH-25nDT_sj3lquQYBWBeD1ESDFmz3mxU4hF0VHN2PcZyuVlKrlbRlsDoM-xZwTDn9IGNh7M-zWHsyw92ZY0LaYUdZe_X3gw9JR_YcPsMh0GzDZ7APOHvuQisq2j-H_DL8Are2alg</recordid><startdate>20090924</startdate><enddate>20090924</enddate><creator>Fabian, Marc R.</creator><creator>Mathonnet, Géraldine</creator><creator>Sundermeier, Thomas</creator><creator>Mathys, Hansruedi</creator><creator>Zipprich, Jakob T.</creator><creator>Svitkin, Yuri V.</creator><creator>Rivas, Fabiola</creator><creator>Jinek, Martin</creator><creator>Wohlschlegel, James</creator><creator>Doudna, Jennifer A.</creator><creator>Chen, Chyi-Ying A.</creator><creator>Shyu, Ann-Bin</creator><creator>Yates, John R.</creator><creator>Hannon, Gregory J.</creator><creator>Filipowicz, Witold</creator><creator>Duchaine, Thomas F.</creator><creator>Sonenberg, Nahum</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090924</creationdate><title>Mammalian miRNA RISC Recruits CAF1 and PABP to Affect PABP-Dependent Deadenylation</title><author>Fabian, Marc R. ; Mathonnet, Géraldine ; Sundermeier, Thomas ; Mathys, Hansruedi ; Zipprich, Jakob T. ; Svitkin, Yuri V. ; Rivas, Fabiola ; Jinek, Martin ; Wohlschlegel, James ; Doudna, Jennifer A. ; Chen, Chyi-Ying A. ; Shyu, Ann-Bin ; Yates, John R. ; Hannon, Gregory J. ; Filipowicz, Witold ; Duchaine, Thomas F. ; Sonenberg, Nahum</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c527t-618c2e9c134b7c77511c628c6f079209ea1932081d596b3846e12363fa88c1e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Argonaute Proteins</topic><topic>Ascites - genetics</topic><topic>Ascites - metabolism</topic><topic>Autoantigens - metabolism</topic><topic>Binding Sites</topic><topic>Carcinoma, Krebs 2 - genetics</topic><topic>Carcinoma, Krebs 2 - metabolism</topic><topic>Cell-Free System</topic><topic>Eukaryotic Initiation Factor-2 - metabolism</topic><topic>Eukaryotic Initiation Factor-4G - metabolism</topic><topic>Gene Silencing</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Mice</topic><topic>MicroRNAs - metabolism</topic><topic>Poly(A)-Binding Proteins - genetics</topic><topic>Poly(A)-Binding Proteins - metabolism</topic><topic>Protein Biosynthesis</topic><topic>Protein Structure, Tertiary</topic><topic>PROTEINS</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Receptors, CCR4 - metabolism</topic><topic>RNA</topic><topic>RNA Processing, Post-Transcriptional</topic><topic>RNA Stability</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA-Induced Silencing Complex - genetics</topic><topic>RNA-Induced Silencing Complex - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fabian, Marc R.</creatorcontrib><creatorcontrib>Mathonnet, Géraldine</creatorcontrib><creatorcontrib>Sundermeier, Thomas</creatorcontrib><creatorcontrib>Mathys, Hansruedi</creatorcontrib><creatorcontrib>Zipprich, Jakob T.</creatorcontrib><creatorcontrib>Svitkin, Yuri V.</creatorcontrib><creatorcontrib>Rivas, Fabiola</creatorcontrib><creatorcontrib>Jinek, Martin</creatorcontrib><creatorcontrib>Wohlschlegel, James</creatorcontrib><creatorcontrib>Doudna, Jennifer A.</creatorcontrib><creatorcontrib>Chen, Chyi-Ying A.</creatorcontrib><creatorcontrib>Shyu, Ann-Bin</creatorcontrib><creatorcontrib>Yates, John R.</creatorcontrib><creatorcontrib>Hannon, Gregory J.</creatorcontrib><creatorcontrib>Filipowicz, Witold</creatorcontrib><creatorcontrib>Duchaine, Thomas F.</creatorcontrib><creatorcontrib>Sonenberg, Nahum</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fabian, Marc R.</au><au>Mathonnet, Géraldine</au><au>Sundermeier, Thomas</au><au>Mathys, Hansruedi</au><au>Zipprich, Jakob T.</au><au>Svitkin, Yuri V.</au><au>Rivas, Fabiola</au><au>Jinek, Martin</au><au>Wohlschlegel, James</au><au>Doudna, Jennifer A.</au><au>Chen, Chyi-Ying A.</au><au>Shyu, Ann-Bin</au><au>Yates, John R.</au><au>Hannon, Gregory J.</au><au>Filipowicz, Witold</au><au>Duchaine, Thomas F.</au><au>Sonenberg, Nahum</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mammalian miRNA RISC Recruits CAF1 and PABP to Affect PABP-Dependent Deadenylation</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2009-09-24</date><risdate>2009</risdate><volume>35</volume><issue>6</issue><spage>868</spage><epage>880</epage><pages>868-880</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>MicroRNAs (miRNAs) inhibit mRNA expression in general by base pairing to the 3′UTR of target mRNAs and consequently inhibiting translation and/or initiating poly(A) tail deadenylation and mRNA destabilization. Here we examine the mechanism and kinetics of miRNA-mediated deadenylation in mouse Krebs-2 ascites extract. We demonstrate that miRNA-mediated mRNA deadenylation occurs subsequent to initial translational inhibition, indicating a two-step mechanism of miRNA action, which serves to consolidate repression. We show that a let-7 miRNA-loaded RNA-induced silencing complex (miRISC) interacts with the poly(A)-binding protein (PABP) and the CAF1 and CCR4 deadenylases. In addition, we demonstrate that miRNA-mediated deadenylation is dependent upon CAF1 activity and PABP, which serves as a bona fide miRNA coactivator. Importantly, we present evidence that GW182, a core component of the miRISC, directly interacts with PABP via its C-terminal region and that this interaction is required for miRNA-mediated deadenylation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19716330</pmid><doi>10.1016/j.molcel.2009.08.004</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Animals Argonaute Proteins Ascites - genetics Ascites - metabolism Autoantigens - metabolism Binding Sites Carcinoma, Krebs 2 - genetics Carcinoma, Krebs 2 - metabolism Cell-Free System Eukaryotic Initiation Factor-2 - metabolism Eukaryotic Initiation Factor-4G - metabolism Gene Silencing HeLa Cells Humans Kinetics Mice MicroRNAs - metabolism Poly(A)-Binding Proteins - genetics Poly(A)-Binding Proteins - metabolism Protein Biosynthesis Protein Structure, Tertiary PROTEINS Proteins - genetics Proteins - metabolism Receptors, CCR4 - metabolism RNA RNA Processing, Post-Transcriptional RNA Stability RNA, Messenger - metabolism RNA-Induced Silencing Complex - genetics RNA-Induced Silencing Complex - metabolism Transfection |
| title | Mammalian miRNA RISC Recruits CAF1 and PABP to Affect PABP-Dependent Deadenylation |
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