{"id":71203,"date":"2024-10-24T10:49:42","date_gmt":"2024-10-24T08:49:42","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=71203"},"modified":"2024-10-24T10:49:49","modified_gmt":"2024-10-24T08:49:49","slug":"the-cellular-superhero-that-protects-us-against-rna-viruses","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science-technology\/the-cellular-superhero-that-protects-us-against-rna-viruses\/","title":{"rendered":"The cellular superhero that protects us against RNA viruses"},"content":{"rendered":"\n<article class=\"vf-card vf-card--brand vf-card--bordered vf-u-margin__bottom--800\" default>\n  <div class=\"vf-card__content | vf-stack vf-stack--400\">\n      <h3 class=\"vf-card__heading\">\n      Summary    <\/h3>\n                <p class=\"vf-card__text\"><ul>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">The innate immune system is the body\u2019s first line of defence against pathogens like bacteria or viruses.\u00a0<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">TRIM25 is a protein that is important in the innate immune response against RNA viruses, such as influenza viruses, coronaviruses, or Zika virus.<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">New research from EMBL has shown how TRIM25 binds to viral RNA and why this binding is essential for its antiviral activity.<\/span><\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n\n\n\n<p>Every second of every day, our body is under attack. The invading agents are viruses, bacteria, parasites, toxins \u2013 living and non-living entities that might negatively impact our body\u2019s functioning. What keeps us safe is a squad of patrolling superheroes \u2013 proteins that form an essential part of our innate immune system, the body\u2019s first line of defence against invaders.&nbsp;<\/p>\n\n\n\n<p><a href=\"https:\/\/www.nature.com\/articles\/s41467-024-52918-x\">A new study<\/a> from EMBL Heidelberg researchers has brought us one step closer to understanding how one such superhero \u2013 a protein called TRIM25 \u2013 exercises its superpowers to fight viruses.&nbsp;<\/p>\n\n\n\n<p>\u201cWe were inspired to study TRIM25 because of its critical role in the body&#8217;s innate immune response to RNA viruses, such as influenza or Zika viruses,\u201d said Luc\u00eda \u00c1lvarez, the study\u2019s first author and <a href=\"https:\/\/www.embl.org\/about\/info\/postdoctoral-programme\/eipod4-fellowship-programme\/\">EIPOD4<\/a> postdoctoral fellow in EMBL\u2019s <a href=\"https:\/\/www.embl.org\/groups\/hennig\/\">Hennig Group<\/a><em>.<\/em> \u201cWe wanted to understand the role of TRIM25\u2019s RNA binding in antiviral defence.\u201d<\/p>\n\n\n\n<p>TRIM25 belongs to a large family of enzymes that can tag other proteins in the cell with a small protein called ubiquitin, altering their function. Its superpower is the ability to trigger a series of signalling events that eventually leads to the foreign agent being identified and neutralised. While scientists had previously shown that TRIM25 can bind RNA, it wasn\u2019t clear why this action is important for its immune activity.\u00a0<\/p>\n\n\n\n<p>TRIM25 also faces the proverbial needle in a haystack problem \u2013 after all, our cells are swimming in RNA, much of it essential for our biology and functioning. So, does TRIM25 have a way to distinguish friend from foe and selectively bind to RNA that comes from viruses?<\/p>\n\n\n\n<p>The scientists used a combination of biophysical and cell biological techniques to investigate this question in more detail. \u201cWe found that TRIM25 doesn&#8217;t just randomly bind to any RNA,\u201d said \u00c1lvarez. \u201cIt has specific preferences, which may explain how it efficiently targets regions of viral RNA.\u201d<\/p>\n\n\n\n<p>The scientists also found that this binding to viral RNA was critical for TRIM25\u2019s antiviral activity, as well as its ability to find its way to \u2018factories\u2019 inside the cell where the virus makes copies of itself. To test this, the researchers created a mutant version of TRIM25, which could not bind RNA. Cells that had this \u2018defective\u2019 version of TRIM25 were less effective in fighting an infection by the Sindbis virus \u2013 an RNA virus that can be transferred from mosquitoes to vertebrates.<\/p>\n\n\n\n<p>The study, recently published <a href=\"https:\/\/www.nature.com\/articles\/s41467-024-52918-x\">in the journal <em>Nature Communications<\/em><\/a>, was carried out in collaboration with Alfredo Castello\u2019s group at the Centre for Virus Research (CVR) in Glasgow. The researchers also worked closely with Fred Allain&#8217;s group at ETH Zurich.<\/p>\n\n\n\n<p>\u201cThis project was made possible by the EIPOD4 grant and the<a href=\"https:\/\/www.embl.org\/about\/info\/infection-biology\/projects\/#vf-tabs__section-ibtt-synergy-projects\"> infection biology transversal theme (IBTT) synergy grant<\/a>, which allowed me to travel from EMBL to CVR to benefit from the synergies between the groups,\u201d said \u00c1lvarez.&nbsp;<\/p>\n\n\n\n<p>As a next step, the researchers are investigating whether TRIM25\u2019s RNA binding is important not just for the Sindbis virus but also for defence against other RNA viruses. The team is also collaborating with <a href=\"https:\/\/www.embl.org\/groups\/mahamid\/\">Julia Mahamid\u2019s group<\/a> at EMBL Heidelberg to use cryo-electron tomography to get a closer look at the viral replication organelles inside cells where TRIM25 localises. A recent German Research Foundation grant, jointly submitted by the two groups, will enable this part of the work.\u00a0<\/p>\n\n\n\n<p>\u201cTRIM25 plays a key role in how our bodies respond to viruses, such as influenza, dengue, and coronaviruses,\u201d said Janosch Hennig, EMBL Visiting Group Leader and the study\u2019s senior author. \u201cBy better understanding how TRIM25 works, we could potentially develop strategies to enhance this immune response, making it a potential target for antiviral therapies. In addition, the study could be applied to wider research into RNA-binding proteins and innate immunity, helping to uncover similar mechanisms in other proteins or immune pathways.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Scientists have discovered how the antiviral protein TRIM25 finds and binds viral RNA to activate an innate immune response.<\/p>\n","protected":false},"author":124,"featured_media":71205,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[17591],"tags":[729,3684,17693,70,1710,659],"embl_taxonomy":[9796,19283,17363,5152],"class_list":["post-71203","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science-technology","tag-hennig","tag-infection-biology","tag-molecular-systems-biology","tag-rna","tag-rna-binding-proteins","tag-virus","embl_taxonomy-embl-heidelberg","embl_taxonomy-hennig-group-visiting","embl_taxonomy-infection-biology","embl_taxonomy-molecular-systems-biology"],"acf":{"vf_locked":false,"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"<p>Scientists have discovered how the antiviral protein TRIM25 finds and binds viral RNA to activate an immune response<\/p>\n","related_links":[{"link_description":"Hennig Group (visiting)\r\n","link_url":"https:\/\/www.embl.org\/groups\/hennig\/"},{"link_description":"Molecular Systems Biology Unit\r\n","link_url":"https:\/\/www.embl.org\/research\/units\/molecular-systems-biology\/"},{"link_description":"Infectional Biology Transversal Theme\r\n","link_url":"https:\/\/www.embl.org\/about\/info\/infection-biology\/"}],"source_article":[{"publication_title":"The molecular dissection of TRIM25\u2019s RNA-binding mechanism provides key insights into its antiviral activity. ","publication_link":{"title":"","url":"https:\/\/www.nature.com\/articles\/s41467-024-52918-x","target":""},"publication_authors":"\u00c1lvarez L., et al.","publication_source":"Nature Communications","publication_date":"1 October 2024","publication_doi":"10.1038\/s41467-024-52918-x"}],"in_this_article":false,"press_contact":"None","article_translations":false,"languages":""},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"b14d3f13-5670-44fb-8970-e54dfd9c921a\";i:1;s:36:\"89e00fee-87f4-482e-a801-4c3548bb6a58\";i:2;s:36:\"ab46b6d4-71d8-49f8-b2f4-b326d4c8ea4e\";}","parents":[],"name":["EMBL Heidelberg"],"slug":"embl-heidelberg","description":"Where &gt; All EMBL sites &gt; EMBL Heidelberg"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"bd910dd7-0cda-4618-8bfa-d37fbda8438e\";i:2;s:36:\"b2b29b9c-72c1-4976-87d1-b7e5d570b84c\";}","parents":[],"name":["Hennig Group (Visiting)"],"slug":"hennig-group-visiting","description":"What &gt; Molecular Systems Biology &gt; Hennig Group (Visiting)"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"e6ac6e6e-6386-48ff-9a0b-618e391d09bb\";i:2;s:36:\"17a828df-c40a-425a-b3e7-dd20d54f7272\";}","parents":[],"name":["Infection Biology"],"slug":"infection-biology","description":"What &gt; Research &gt; Infection Biology"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"7ca3ce91-dc32-47ea-8d4b-7a53c3a3a9fd\";i:2;s:36:\"bd910dd7-0cda-4618-8bfa-d37fbda8438e\";}","parents":[],"name":["Molecular Systems Biology"],"slug":"molecular-systems-biology","description":"What &gt; Research Units &gt; Molecular Systems Biology"}],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>The cellular superhero that protects us against RNA viruses | EMBL<\/title>\n<meta name=\"description\" content=\"Scientists have discovered how the antiviral protein TRIM25 finds and binds viral RNA to activate an innate immune response.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science-technology\/the-cellular-superhero-that-protects-us-against-rna-viruses\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The cellular superhero that protects us against RNA viruses | EMBL\" \/>\n<meta property=\"og:description\" content=\"Scientists have discovered how the antiviral protein TRIM25 finds and binds viral RNA to activate an innate immune response.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science-technology\/the-cellular-superhero-that-protects-us-against-rna-viruses\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2024-10-24T08:49:42+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-10-24T08:49:49+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/10\/TRIM25-.png\" \/>\n\t<meta property=\"og:image:width\" content=\"1000\" \/>\n\t<meta property=\"og:image:height\" content=\"600\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"author\" content=\"Shreya Ghosh\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@embl\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Shreya Ghosh\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/the-cellular-superhero-that-protects-us-against-rna-viruses\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/the-cellular-superhero-that-protects-us-against-rna-viruses\/\"},\"author\":{\"name\":\"Shreya Ghosh\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/de071e57de42c03b5f23d1e391048fb2\"},\"headline\":\"The cellular superhero that protects us against RNA viruses\",\"datePublished\":\"2024-10-24T08:49:42+00:00\",\"dateModified\":\"2024-10-24T08:49:49+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/the-cellular-superhero-that-protects-us-against-rna-viruses\/\"},\"wordCount\":649,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/the-cellular-superhero-that-protects-us-against-rna-viruses\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/10\/TRIM25-.png\",\"keywords\":[\"hennig\",\"infection biology\",\"molecular systems biology\",\"rna\",\"rna-binding proteins\",\"virus\"],\"articleSection\":[\"Science &amp; 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TRIM25 (green, left) finds its way to the same locations in the cell where a virus (red, middle) replicates. The image on the right shows how the two overlap. 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