Investigating the correlation between Xrn1-resistant RNAs and frameshifter pseudoknots
Xrn1-resistant RNA structures are multifunctional elements employed by an increasing number of RNA viruses. One of such elements is the coremin motif, discovered in plant virus RNAs, of which the structure has been hypothesized to form a yet unelucidated pseudoknot. Recently, the coremin motif was s...
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| Veröffentlicht in: | RNA biology 2023-12, Vol.20 (1), p.409-418 |
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| creator | Dilweg, Ivar W. Oskam, Megan G. Overbeek, Sophie Olsthoorn, René C.L. |
| description | Xrn1-resistant RNA structures are multifunctional elements employed by an increasing number of RNA viruses. One of such elements is the coremin motif, discovered in plant virus RNAs, of which the structure has been hypothesized to form a yet unelucidated pseudoknot. Recently, the coremin motif was shown to be capable of stalling not only Xrn1, but scanning ribosomes as well. Following that observation, in this study we demonstrate that the coremin motif can promote −1 ribosomal frameshifting, similar to better-characterized viral frameshifting pseudoknots. Since this function was lost in concert with substitutions that were known to disturb Xrn1-resistance, we developed a frameshifting screen for finding novel Xrn1-resistant RNAs by randomizing parts of the coremin motif. This yielded new insights into the coremin motif structure, as Xrn1-resistant variations were identified that more clearly indicate a pseudoknot interaction. In addition, we show that the Xrn1-resistant RNA of Zika virus promotes frameshifting as well, while known −1 programmed ribosomal frameshifting pseudoknots do not stall Xrn1, suggesting that promoting frameshifting is a universal characteristic of Xrn1-resistant RNAs, but that Xrn1-resistance requires more than just a frameshifting pseudoknot. |
| doi_str_mv | 10.1080/15476286.2023.2205224 |
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One of such elements is the coremin motif, discovered in plant virus RNAs, of which the structure has been hypothesized to form a yet unelucidated pseudoknot. Recently, the coremin motif was shown to be capable of stalling not only Xrn1, but scanning ribosomes as well. Following that observation, in this study we demonstrate that the coremin motif can promote −1 ribosomal frameshifting, similar to better-characterized viral frameshifting pseudoknots. Since this function was lost in concert with substitutions that were known to disturb Xrn1-resistance, we developed a frameshifting screen for finding novel Xrn1-resistant RNAs by randomizing parts of the coremin motif. This yielded new insights into the coremin motif structure, as Xrn1-resistant variations were identified that more clearly indicate a pseudoknot interaction. In addition, we show that the Xrn1-resistant RNA of Zika virus promotes frameshifting as well, while known −1 programmed ribosomal frameshifting pseudoknots do not stall Xrn1, suggesting that promoting frameshifting is a universal characteristic of Xrn1-resistant RNAs, but that Xrn1-resistance requires more than just a frameshifting pseudoknot.</description><identifier>ISSN: 1547-6286</identifier><identifier>ISSN: 1555-8584</identifier><identifier>EISSN: 1555-8584</identifier><identifier>DOI: 10.1080/15476286.2023.2205224</identifier><identifier>PMID: 37400999</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Base Sequence ; Biological Sciences ; coremin motif ; Frameshifting, Ribosomal ; Humans ; Nucleic Acid Conformation ; Research Paper ; ribosomal frameshifting ; ribosomes ; Ribosomes - metabolism ; RNA ; RNA pseudoknot ; RNA, Viral - metabolism ; viruses ; Xrn1 ; Zika virus ; Zika Virus - genetics ; Zika Virus Infection - genetics</subject><ispartof>RNA biology, 2023-12, Vol.20 (1), p.409-418</ispartof><rights>2023 The Author(s). 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One of such elements is the coremin motif, discovered in plant virus RNAs, of which the structure has been hypothesized to form a yet unelucidated pseudoknot. Recently, the coremin motif was shown to be capable of stalling not only Xrn1, but scanning ribosomes as well. Following that observation, in this study we demonstrate that the coremin motif can promote −1 ribosomal frameshifting, similar to better-characterized viral frameshifting pseudoknots. Since this function was lost in concert with substitutions that were known to disturb Xrn1-resistance, we developed a frameshifting screen for finding novel Xrn1-resistant RNAs by randomizing parts of the coremin motif. This yielded new insights into the coremin motif structure, as Xrn1-resistant variations were identified that more clearly indicate a pseudoknot interaction. In addition, we show that the Xrn1-resistant RNA of Zika virus promotes frameshifting as well, while known −1 programmed ribosomal frameshifting pseudoknots do not stall Xrn1, suggesting that promoting frameshifting is a universal characteristic of Xrn1-resistant RNAs, but that Xrn1-resistance requires more than just a frameshifting pseudoknot.</description><subject>Base Sequence</subject><subject>Biological Sciences</subject><subject>coremin motif</subject><subject>Frameshifting, Ribosomal</subject><subject>Humans</subject><subject>Nucleic Acid Conformation</subject><subject>Research Paper</subject><subject>ribosomal frameshifting</subject><subject>ribosomes</subject><subject>Ribosomes - metabolism</subject><subject>RNA</subject><subject>RNA pseudoknot</subject><subject>RNA, Viral - metabolism</subject><subject>viruses</subject><subject>Xrn1</subject><subject>Zika virus</subject><subject>Zika Virus - genetics</subject><subject>Zika Virus Infection - genetics</subject><issn>1547-6286</issn><issn>1555-8584</issn><issn>1555-8584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqFkk1v1DAQhiMEomXhJ4By5JLFHn_EOUFVFVipAgkB4mY59ng3JWsvtrdV_z0Ju63oBU7-mHcez3jeqnpJyZISRd5QwVsJSi6BAFsCEAHAH1WnVAjRKKH443nP22YWnVTPcr4ihEnViafVCWs5IV3XnVbfV-EacxnWpgxhXZcN1jamhON0jqHusdwghvpHCrRJmIdcTCj1l09nuTbB1T6ZLebN4Aumepdx7-LPEEt-Xj3xZsz44rguqm_vL76ef2wuP39YnZ9dNlZQWRrwwinJFHBiHfQAHUEGgljvOtV5ZFQS2_XeSd4CIVJ5NNIioaYzfWs7tqhWB66L5krv0rA16VZHM-g_FzGttUllsCNq8AooQu-c5RwpzHzsbWutB9NKOrHeHli7fb9FZzGUZMYH0IeRMGz0Ol5rShhQ2rKJ8PpISPHXfvpWvR2yxXE0AeM-a0Y4YZ1kwP8rBcUYATGrF5U4SG2KOSf09yVRomcv6Dsv6NkL-uiFKe_V3_3cZ90NfxK8OwiG4GPampuYRqeLuR1jmgYb7DCV_O83fgOBpcUC</recordid><startdate>20231231</startdate><enddate>20231231</enddate><creator>Dilweg, Ivar W.</creator><creator>Oskam, Megan G.</creator><creator>Overbeek, Sophie</creator><creator>Olsthoorn, René C.L.</creator><general>Taylor & Francis</general><general>Taylor & Francis Group</general><scope>0YH</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>7S9</scope><scope>L.6</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-0315-3005</orcidid></search><sort><creationdate>20231231</creationdate><title>Investigating the correlation between Xrn1-resistant RNAs and frameshifter pseudoknots</title><author>Dilweg, Ivar W. ; Oskam, Megan G. ; Overbeek, Sophie ; Olsthoorn, René C.L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c516t-2f5d8638240cd2b2290e3250cfd989fe3160c9bfd64720068fea6ce01a9ab7c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Base Sequence</topic><topic>Biological Sciences</topic><topic>coremin motif</topic><topic>Frameshifting, Ribosomal</topic><topic>Humans</topic><topic>Nucleic Acid Conformation</topic><topic>Research Paper</topic><topic>ribosomal frameshifting</topic><topic>ribosomes</topic><topic>Ribosomes - metabolism</topic><topic>RNA</topic><topic>RNA pseudoknot</topic><topic>RNA, Viral - metabolism</topic><topic>viruses</topic><topic>Xrn1</topic><topic>Zika virus</topic><topic>Zika Virus - genetics</topic><topic>Zika Virus Infection - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dilweg, Ivar W.</creatorcontrib><creatorcontrib>Oskam, Megan G.</creatorcontrib><creatorcontrib>Overbeek, Sophie</creatorcontrib><creatorcontrib>Olsthoorn, René C.L.</creatorcontrib><collection>Taylor & Francis 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>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>RNA biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dilweg, Ivar W.</au><au>Oskam, Megan G.</au><au>Overbeek, Sophie</au><au>Olsthoorn, René C.L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigating the correlation between Xrn1-resistant RNAs and frameshifter pseudoknots</atitle><jtitle>RNA biology</jtitle><addtitle>RNA Biol</addtitle><date>2023-12-31</date><risdate>2023</risdate><volume>20</volume><issue>1</issue><spage>409</spage><epage>418</epage><pages>409-418</pages><issn>1547-6286</issn><issn>1555-8584</issn><eissn>1555-8584</eissn><abstract>Xrn1-resistant RNA structures are multifunctional elements employed by an increasing number of RNA viruses. 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In addition, we show that the Xrn1-resistant RNA of Zika virus promotes frameshifting as well, while known −1 programmed ribosomal frameshifting pseudoknots do not stall Xrn1, suggesting that promoting frameshifting is a universal characteristic of Xrn1-resistant RNAs, but that Xrn1-resistance requires more than just a frameshifting pseudoknot.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>37400999</pmid><doi>10.1080/15476286.2023.2205224</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-0315-3005</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Base Sequence Biological Sciences coremin motif Frameshifting, Ribosomal Humans Nucleic Acid Conformation Research Paper ribosomal frameshifting ribosomes Ribosomes - metabolism RNA RNA pseudoknot RNA, Viral - metabolism viruses Xrn1 Zika virus Zika Virus - genetics Zika Virus Infection - genetics |
| title | Investigating the correlation between Xrn1-resistant RNAs and frameshifter pseudoknots |
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