On the Role of RNA Amplification in dsRNA-Triggered Gene Silencing
We have investigated the role of trigger RNA amplification during RNA interference (RNAi) in Caenorhabditis elegans. Analysis of small interfering RNAs (siRNAs) produced during RNAi in C. elegans revealed a substantial fraction that cannot derive directly from input dsRNA. Instead, a population of s...
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| Veröffentlicht in: | Cell 2001-11, Vol.107 (4), p.465-476 |
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| creator | Sijen, Titia Fleenor, Jamie Simmer, Femke Thijssen, Karen L. Parrish, Susan Timmons, Lisa Plasterk, Ronald H.A. Fire, Andrew |
| description | We have investigated the role of trigger RNA amplification during RNA interference (RNAi) in Caenorhabditis elegans. Analysis of small interfering RNAs (siRNAs) produced during RNAi in C. elegans revealed a substantial fraction that cannot derive directly from input dsRNA. Instead, a population of siRNAs (termed secondary siRNAs) appeared to derive from the action of a cellular RNA-directed RNA polymerase (RdRP) on mRNAs that are being targeted by the RNAi mechanism. The distribution of secondary siRNAs exhibited a distinct polarity (5′→3′ on the antisense strand), suggesting a cyclic amplification process in which RdRP is primed by existing siRNAs. This amplification mechanism substantially augments the potency of RNAi-based surveillance, while ensuring that the RNAi machinery will focus on expressed mRNAs. |
| doi_str_mv | 10.1016/S0092-8674(01)00576-1 |
| format | Article |
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Analysis of small interfering RNAs (siRNAs) produced during RNAi in C. elegans revealed a substantial fraction that cannot derive directly from input dsRNA. Instead, a population of siRNAs (termed secondary siRNAs) appeared to derive from the action of a cellular RNA-directed RNA polymerase (RdRP) on mRNAs that are being targeted by the RNAi mechanism. The distribution of secondary siRNAs exhibited a distinct polarity (5′→3′ on the antisense strand), suggesting a cyclic amplification process in which RdRP is primed by existing siRNAs. This amplification mechanism substantially augments the potency of RNAi-based surveillance, while ensuring that the RNAi machinery will focus on expressed mRNAs.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/S0092-8674(01)00576-1</identifier><identifier>PMID: 11719187</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Animals, Genetically Modified ; Bacterial Proteins ; Caenorhabditis elegans ; Caenorhabditis elegans - embryology ; Caenorhabditis elegans - genetics ; Endoribonucleases - physiology ; Gene Silencing - physiology ; Helminth Proteins - genetics ; Helminth Proteins - physiology ; Models, Genetic ; Recombinant Fusion Proteins - physiology ; Ribonuclease III ; RNA, Double-Stranded - physiology ; RNA, Helminth - physiology ; RNA, Small Interfering ; RNA, Untranslated - physiology ; RNA-Directed DNA Polymerase - physiology ; Sequence Deletion ; Transcription Factors - genetics ; Transcription Factors - physiology ; Transgenes</subject><ispartof>Cell, 2001-11, Vol.107 (4), p.465-476</ispartof><rights>2001 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-70a71ecbfbc45dca07aa63b3ac1fd23eb464715f088c4348b07e86b2f22238ed3</citedby><cites>FETCH-LOGICAL-c557t-70a71ecbfbc45dca07aa63b3ac1fd23eb464715f088c4348b07e86b2f22238ed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0092867401005761$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11719187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sijen, Titia</creatorcontrib><creatorcontrib>Fleenor, Jamie</creatorcontrib><creatorcontrib>Simmer, Femke</creatorcontrib><creatorcontrib>Thijssen, Karen L.</creatorcontrib><creatorcontrib>Parrish, Susan</creatorcontrib><creatorcontrib>Timmons, Lisa</creatorcontrib><creatorcontrib>Plasterk, Ronald H.A.</creatorcontrib><creatorcontrib>Fire, Andrew</creatorcontrib><title>On the Role of RNA Amplification in dsRNA-Triggered Gene Silencing</title><title>Cell</title><addtitle>Cell</addtitle><description>We have investigated the role of trigger RNA amplification during RNA interference (RNAi) in Caenorhabditis elegans. 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This amplification mechanism substantially augments the potency of RNAi-based surveillance, while ensuring that the RNAi machinery will focus on expressed mRNAs.</description><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Bacterial Proteins</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - embryology</subject><subject>Caenorhabditis elegans - genetics</subject><subject>Endoribonucleases - physiology</subject><subject>Gene Silencing - physiology</subject><subject>Helminth Proteins - genetics</subject><subject>Helminth Proteins - physiology</subject><subject>Models, Genetic</subject><subject>Recombinant Fusion Proteins - physiology</subject><subject>Ribonuclease III</subject><subject>RNA, Double-Stranded - physiology</subject><subject>RNA, Helminth - physiology</subject><subject>RNA, Small Interfering</subject><subject>RNA, Untranslated - physiology</subject><subject>RNA-Directed DNA Polymerase - physiology</subject><subject>Sequence Deletion</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - physiology</subject><subject>Transgenes</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLxDAUhYMoOj5-gpKV6KJ6b9o06UpG8QWi4GMd0vR2jHTaMekI_ns7D3Tp6sLlO-fAx9ghwhkC5ucvAIVIdK6yE8BTAKnyBDfYCKFQSYZKbLLRL7LDdmP8AAAtpdxmO4gKC9RqxC6fWt6_E3_uGuJdzZ8fx3w8nTW-9s72vmu5b3kVh3fyGvxkQoEqfkst8RffUOt8O9lnW7VtIh2s7x57u7l-vbpLHp5u76_GD4mTUvWJAquQXFmXLpOVs6CszdMytQ7rSqRUZnmmUNagtcvSTJegSOelqIUQqaYq3WPHq95Z6D7nFHsz9dFR09iWunk0SohCpEr_C6IWWMgcB1CuQBe6GAPVZhb81IZvg2AWls3SslkoNIBmadksckfrgXk5peovtdY6ABcrgAYfX56Cic4PtqjygVxvqs7_M_EDPDuKTA</recordid><startdate>20011116</startdate><enddate>20011116</enddate><creator>Sijen, Titia</creator><creator>Fleenor, Jamie</creator><creator>Simmer, Femke</creator><creator>Thijssen, Karen L.</creator><creator>Parrish, Susan</creator><creator>Timmons, Lisa</creator><creator>Plasterk, Ronald H.A.</creator><creator>Fire, Andrew</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20011116</creationdate><title>On the Role of RNA Amplification in dsRNA-Triggered Gene Silencing</title><author>Sijen, Titia ; Fleenor, Jamie ; Simmer, Femke ; Thijssen, Karen L. ; Parrish, Susan ; Timmons, Lisa ; Plasterk, Ronald H.A. ; Fire, Andrew</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-70a71ecbfbc45dca07aa63b3ac1fd23eb464715f088c4348b07e86b2f22238ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Bacterial Proteins</topic><topic>Caenorhabditis elegans</topic><topic>Caenorhabditis elegans - embryology</topic><topic>Caenorhabditis elegans - genetics</topic><topic>Endoribonucleases - physiology</topic><topic>Gene Silencing - physiology</topic><topic>Helminth Proteins - genetics</topic><topic>Helminth Proteins - physiology</topic><topic>Models, Genetic</topic><topic>Recombinant Fusion Proteins - physiology</topic><topic>Ribonuclease III</topic><topic>RNA, Double-Stranded - physiology</topic><topic>RNA, Helminth - physiology</topic><topic>RNA, Small Interfering</topic><topic>RNA, Untranslated - physiology</topic><topic>RNA-Directed DNA Polymerase - physiology</topic><topic>Sequence Deletion</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - physiology</topic><topic>Transgenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sijen, Titia</creatorcontrib><creatorcontrib>Fleenor, Jamie</creatorcontrib><creatorcontrib>Simmer, Femke</creatorcontrib><creatorcontrib>Thijssen, Karen L.</creatorcontrib><creatorcontrib>Parrish, Susan</creatorcontrib><creatorcontrib>Timmons, Lisa</creatorcontrib><creatorcontrib>Plasterk, Ronald H.A.</creatorcontrib><creatorcontrib>Fire, Andrew</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>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sijen, Titia</au><au>Fleenor, Jamie</au><au>Simmer, Femke</au><au>Thijssen, Karen L.</au><au>Parrish, Susan</au><au>Timmons, Lisa</au><au>Plasterk, Ronald H.A.</au><au>Fire, Andrew</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>On the Role of RNA Amplification in dsRNA-Triggered Gene Silencing</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2001-11-16</date><risdate>2001</risdate><volume>107</volume><issue>4</issue><spage>465</spage><epage>476</epage><pages>465-476</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>We have investigated the role of trigger RNA amplification during RNA interference (RNAi) in Caenorhabditis elegans. Analysis of small interfering RNAs (siRNAs) produced during RNAi in C. elegans revealed a substantial fraction that cannot derive directly from input dsRNA. Instead, a population of siRNAs (termed secondary siRNAs) appeared to derive from the action of a cellular RNA-directed RNA polymerase (RdRP) on mRNAs that are being targeted by the RNAi mechanism. The distribution of secondary siRNAs exhibited a distinct polarity (5′→3′ on the antisense strand), suggesting a cyclic amplification process in which RdRP is primed by existing siRNAs. This amplification mechanism substantially augments the potency of RNAi-based surveillance, while ensuring that the RNAi machinery will focus on expressed mRNAs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11719187</pmid><doi>10.1016/S0092-8674(01)00576-1</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Genetically Modified Bacterial Proteins Caenorhabditis elegans Caenorhabditis elegans - embryology Caenorhabditis elegans - genetics Endoribonucleases - physiology Gene Silencing - physiology Helminth Proteins - genetics Helminth Proteins - physiology Models, Genetic Recombinant Fusion Proteins - physiology Ribonuclease III RNA, Double-Stranded - physiology RNA, Helminth - physiology RNA, Small Interfering RNA, Untranslated - physiology RNA-Directed DNA Polymerase - physiology Sequence Deletion Transcription Factors - genetics Transcription Factors - physiology Transgenes |
| title | On the Role of RNA Amplification in dsRNA-Triggered Gene Silencing |
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