3' Uridylation controls mature microRNA turnover during CD4 T-cell activation
Activation of T lymphocytes requires a tight regulation of microRNA (miRNA) expression. Terminal uridyltransferases (TUTases) catalyze 3' nontemplated nucleotide addition (3'NTA) to miRNAs, which may influence miRNA stability and function. Here, we investigated 3'NTA to mature miRNA i...
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Veröffentlicht in: | RNA (Cambridge) 2017-06, Vol.23 (6), p.882-891 |
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creator | Gutiérrez-Vázquez, Cristina Enright, Anton J Rodríguez-Galán, Ana Pérez-García, Arantxa Collier, Paul Jones, Matthew R Benes, Vladimir Mizgerd, Joseph P Mittelbrunn, María Ramiro, Almudena R Sánchez-Madrid, Francisco |
description | Activation of T lymphocytes requires a tight regulation of microRNA (miRNA) expression. Terminal uridyltransferases (TUTases) catalyze 3' nontemplated nucleotide addition (3'NTA) to miRNAs, which may influence miRNA stability and function. Here, we investigated 3'NTA to mature miRNA in CD4 T lymphocytes by deep sequencing. Upon T-cell activation, miRNA sequences bearing terminal uridines are specifically decreased, concomitantly with down-regulation of TUT4 and TUT7 enzymes. Analyzing TUT4-deficient T lymphocytes, we proved that this terminal uridyltransferase is essential for the maintenance of miRNA uridylation in the steady state of T lymphocytes. Analysis of synthetic uridylated miRNAs shows that 3' addition of uridine promotes degradation of these uridylated miRNAs after T-cell activation. Our data underline post-transcriptional uridylation as a mechanism to fine-tune miRNA levels during T-cell activation. |
doi_str_mv | 10.1261/rna.060095.116 |
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Terminal uridyltransferases (TUTases) catalyze 3' nontemplated nucleotide addition (3'NTA) to miRNAs, which may influence miRNA stability and function. Here, we investigated 3'NTA to mature miRNA in CD4 T lymphocytes by deep sequencing. Upon T-cell activation, miRNA sequences bearing terminal uridines are specifically decreased, concomitantly with down-regulation of TUT4 and TUT7 enzymes. Analyzing TUT4-deficient T lymphocytes, we proved that this terminal uridyltransferase is essential for the maintenance of miRNA uridylation in the steady state of T lymphocytes. Analysis of synthetic uridylated miRNAs shows that 3' addition of uridine promotes degradation of these uridylated miRNAs after T-cell activation. Our data underline post-transcriptional uridylation as a mechanism to fine-tune miRNA levels during T-cell activation.</description><identifier>ISSN: 1355-8382</identifier><identifier>EISSN: 1469-9001</identifier><identifier>DOI: 10.1261/rna.060095.116</identifier><identifier>PMID: 28351886</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Animals ; Antiretroviral drugs ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Cell activation ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Gene Expression Regulation ; Humans ; Lymphocyte Activation - genetics ; Lymphocyte Activation - immunology ; Lymphocytes ; Lymphocytes T ; Mice ; Mice, Knockout ; MicroRNAs ; MicroRNAs - chemistry ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Models, Biological ; Post-transcription ; RNA Stability ; Uridine ; Uridine - chemistry ; Uridine - metabolism</subject><ispartof>RNA (Cambridge), 2017-06, Vol.23 (6), p.882-891</ispartof><rights>2017 Gutiérrez-Vázquez et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.</rights><rights>Copyright Cold Spring Harbor Laboratory Press Jun 2017</rights><rights>2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-ba9dfe0111d9acba46fb567b57e82bccab9cc980aec3bb4cbba89a95651d4a2c3</citedby><cites>FETCH-LOGICAL-c418t-ba9dfe0111d9acba46fb567b57e82bccab9cc980aec3bb4cbba89a95651d4a2c3</cites><orcidid>0000-0002-3846-4631</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435861/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435861/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28351886$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gutiérrez-Vázquez, Cristina</creatorcontrib><creatorcontrib>Enright, Anton J</creatorcontrib><creatorcontrib>Rodríguez-Galán, Ana</creatorcontrib><creatorcontrib>Pérez-García, Arantxa</creatorcontrib><creatorcontrib>Collier, Paul</creatorcontrib><creatorcontrib>Jones, Matthew R</creatorcontrib><creatorcontrib>Benes, Vladimir</creatorcontrib><creatorcontrib>Mizgerd, Joseph P</creatorcontrib><creatorcontrib>Mittelbrunn, María</creatorcontrib><creatorcontrib>Ramiro, Almudena R</creatorcontrib><creatorcontrib>Sánchez-Madrid, Francisco</creatorcontrib><title>3' Uridylation controls mature microRNA turnover during CD4 T-cell activation</title><title>RNA (Cambridge)</title><addtitle>RNA</addtitle><description>Activation of T lymphocytes requires a tight regulation of microRNA (miRNA) expression. Terminal uridyltransferases (TUTases) catalyze 3' nontemplated nucleotide addition (3'NTA) to miRNAs, which may influence miRNA stability and function. Here, we investigated 3'NTA to mature miRNA in CD4 T lymphocytes by deep sequencing. Upon T-cell activation, miRNA sequences bearing terminal uridines are specifically decreased, concomitantly with down-regulation of TUT4 and TUT7 enzymes. Analyzing TUT4-deficient T lymphocytes, we proved that this terminal uridyltransferase is essential for the maintenance of miRNA uridylation in the steady state of T lymphocytes. Analysis of synthetic uridylated miRNAs shows that 3' addition of uridine promotes degradation of these uridylated miRNAs after T-cell activation. Our data underline post-transcriptional uridylation as a mechanism to fine-tune miRNA levels during T-cell activation.</description><subject>Animals</subject><subject>Antiretroviral drugs</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cell activation</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Lymphocyte Activation - genetics</subject><subject>Lymphocyte Activation - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>MicroRNAs</subject><subject>MicroRNAs - chemistry</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Models, Biological</subject><subject>Post-transcription</subject><subject>RNA Stability</subject><subject>Uridine</subject><subject>Uridine - chemistry</subject><subject>Uridine - metabolism</subject><issn>1355-8382</issn><issn>1469-9001</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUU1r3DAUFKWl-WivPQZBD8nFGz3L0kqXQth8QtJCyZ7Fk6xNFGwrleyF_Pso3XRJetLHmxnezBDyDdgMagnHacAZk4xpMQOQH8guNFJXmjH4WO5ciEpxVe-QvZwfyicv489kp1ZcgFJyl9zwQ7pMoX3qcAxxoC4OY4pdpj2OU_K0Dy7F3z9PaHkNce0TbacUhju6OG3obeV811F0Y1j_pX8hn1bYZf_19dwny_Oz28Vldf3r4mpxcl25BtRYWdTtyjMAaDU6i41cWSHnVsy9qq1zaLVzWjH0jlvbOGtRadRCCmgbrB3fJz82uo-T7X3rfFkaO_OYQo_pyUQM5v1kCPfmLq6NaLhQEorA0atAin8mn0fTh_xiBgcfp2xKODVTwOumQL__B32IJYtiz9TAFZuX8OcFNdugSlw5J7_aLgPMvDRlCsVsmjKlqUI4eGthC_9XDX8GxwKQoA</recordid><startdate>201706</startdate><enddate>201706</enddate><creator>Gutiérrez-Vázquez, Cristina</creator><creator>Enright, Anton J</creator><creator>Rodríguez-Galán, Ana</creator><creator>Pérez-García, Arantxa</creator><creator>Collier, Paul</creator><creator>Jones, Matthew R</creator><creator>Benes, Vladimir</creator><creator>Mizgerd, Joseph P</creator><creator>Mittelbrunn, María</creator><creator>Ramiro, Almudena R</creator><creator>Sánchez-Madrid, Francisco</creator><general>Cold Spring Harbor Laboratory Press</general><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>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3846-4631</orcidid></search><sort><creationdate>201706</creationdate><title>3' Uridylation controls mature microRNA turnover during CD4 T-cell activation</title><author>Gutiérrez-Vázquez, Cristina ; Enright, Anton J ; Rodríguez-Galán, Ana ; Pérez-García, Arantxa ; Collier, Paul ; Jones, Matthew R ; Benes, Vladimir ; Mizgerd, Joseph P ; Mittelbrunn, María ; Ramiro, Almudena R ; Sánchez-Madrid, Francisco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-ba9dfe0111d9acba46fb567b57e82bccab9cc980aec3bb4cbba89a95651d4a2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antiretroviral drugs</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cell activation</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Lymphocyte Activation - genetics</topic><topic>Lymphocyte Activation - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>MicroRNAs</topic><topic>MicroRNAs - chemistry</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Models, Biological</topic><topic>Post-transcription</topic><topic>RNA Stability</topic><topic>Uridine</topic><topic>Uridine - chemistry</topic><topic>Uridine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gutiérrez-Vázquez, Cristina</creatorcontrib><creatorcontrib>Enright, Anton J</creatorcontrib><creatorcontrib>Rodríguez-Galán, Ana</creatorcontrib><creatorcontrib>Pérez-García, Arantxa</creatorcontrib><creatorcontrib>Collier, Paul</creatorcontrib><creatorcontrib>Jones, Matthew R</creatorcontrib><creatorcontrib>Benes, Vladimir</creatorcontrib><creatorcontrib>Mizgerd, Joseph P</creatorcontrib><creatorcontrib>Mittelbrunn, María</creatorcontrib><creatorcontrib>Ramiro, Almudena R</creatorcontrib><creatorcontrib>Sánchez-Madrid, Francisco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RNA (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gutiérrez-Vázquez, Cristina</au><au>Enright, Anton J</au><au>Rodríguez-Galán, Ana</au><au>Pérez-García, Arantxa</au><au>Collier, Paul</au><au>Jones, Matthew R</au><au>Benes, Vladimir</au><au>Mizgerd, Joseph P</au><au>Mittelbrunn, María</au><au>Ramiro, Almudena R</au><au>Sánchez-Madrid, Francisco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3' Uridylation controls mature microRNA turnover during CD4 T-cell activation</atitle><jtitle>RNA (Cambridge)</jtitle><addtitle>RNA</addtitle><date>2017-06</date><risdate>2017</risdate><volume>23</volume><issue>6</issue><spage>882</spage><epage>891</epage><pages>882-891</pages><issn>1355-8382</issn><eissn>1469-9001</eissn><abstract>Activation of T lymphocytes requires a tight regulation of microRNA (miRNA) expression. Terminal uridyltransferases (TUTases) catalyze 3' nontemplated nucleotide addition (3'NTA) to miRNAs, which may influence miRNA stability and function. Here, we investigated 3'NTA to mature miRNA in CD4 T lymphocytes by deep sequencing. Upon T-cell activation, miRNA sequences bearing terminal uridines are specifically decreased, concomitantly with down-regulation of TUT4 and TUT7 enzymes. Analyzing TUT4-deficient T lymphocytes, we proved that this terminal uridyltransferase is essential for the maintenance of miRNA uridylation in the steady state of T lymphocytes. Analysis of synthetic uridylated miRNAs shows that 3' addition of uridine promotes degradation of these uridylated miRNAs after T-cell activation. 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subjects | Animals Antiretroviral drugs CD4 antigen CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell activation DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Gene Expression Regulation Humans Lymphocyte Activation - genetics Lymphocyte Activation - immunology Lymphocytes Lymphocytes T Mice Mice, Knockout MicroRNAs MicroRNAs - chemistry MicroRNAs - genetics MicroRNAs - metabolism miRNA Models, Biological Post-transcription RNA Stability Uridine Uridine - chemistry Uridine - metabolism |
title | 3' Uridylation controls mature microRNA turnover during CD4 T-cell activation |
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