{"id":37618,"date":"2026-05-26T16:05:00","date_gmt":"2026-05-26T16:05:00","guid":{"rendered":"https:\/\/www.tun.com\/home\/?p=37618"},"modified":"2026-05-26T19:45:40","modified_gmt":"2026-05-26T19:45:40","slug":"ohio-state-unlocks-25-year-mystery-of-rna-interference-mechanics","status":"publish","type":"post","link":"https:\/\/www.tun.com\/home\/ohio-state-unlocks-25-year-mystery-of-rna-interference-mechanics\/","title":{"rendered":"Ohio State Unlocks 25-Year Mystery of RNA Interference Mechanics"},"content":{"rendered":"\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-uagb-blockquote uagb-block-e7eb3fc3 uagb-blockquote__skin-border uagb-blockquote__stack-img-none\"><blockquote class=\"uagb-blockquote\"><div class=\"uagb-blockquote__content\">A new Ohio State University study is the first to detail how a key protein builds the molecular complex responsible for RNA interference \u2014 a gene-regulating process discovered over two decades ago. The findings could reshape how scientists design gene-silencing therapies for disease.<\/div><footer><div class=\"uagb-blockquote__author-wrap uagb-blockquote__author-at-left\"><\/div><\/footer><\/blockquote><\/div>\n\n\n\n<div class=\"wp-block-group is-content-justification-space-between is-nowrap is-layout-flex wp-container-core-group-is-layout-b0ffac9c wp-block-group-is-layout-flex\"><div style=\"font-size:16px\" class=\"has-text-align-left wp-block-post-author\"><div class=\"wp-block-post-author__content\"><p class=\"wp-block-post-author__name\">The University Network<\/p><\/div><\/div>\n\n\n<div class=\"wp-block-uagb-social-share uagb-social-share__outer-wrap uagb-social-share__layout-horizontal uagb-block-ee584a31\">\n<div class=\"wp-block-uagb-social-share-child uagb-ss-repeater uagb-ss__wrapper uagb-block-ec619ce7\"><span class=\"uagb-ss__link\" data-href=\"https:\/\/www.facebook.com\/sharer.php?u=\" tabindex=\"0\" role=\"button\" aria-label=\"facebook\"><span class=\"uagb-ss__source-wrap\"><span class=\"uagb-ss__source-icon\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" viewBox=\"0 0 512 512\"><path d=\"M504 256C504 119 393 8 256 8S8 119 8 256c0 123.8 90.69 226.4 209.3 245V327.7h-63V256h63v-54.64c0-62.15 37-96.48 93.67-96.48 27.14 0 55.52 4.84 55.52 4.84v61h-31.28c-30.8 0-40.41 19.12-40.41 38.73V256h68.78l-11 71.69h-57.78V501C413.3 482.4 504 379.8 504 256z\"><\/path><\/svg><\/span><\/span><\/span><\/div>\n\n\n\n<div class=\"wp-block-uagb-social-share-child uagb-ss-repeater uagb-ss__wrapper uagb-block-32d99934\"><span class=\"uagb-ss__link\" data-href=\"https:\/\/twitter.com\/share?url=\" tabindex=\"0\" role=\"button\" aria-label=\"twitter\"><span class=\"uagb-ss__source-wrap\"><span class=\"uagb-ss__source-icon\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" viewBox=\"0 0 512 512\"><path d=\"M389.2 48h70.6L305.6 224.2 487 464H345L233.7 318.6 106.5 464H35.8L200.7 275.5 26.8 48H172.4L272.9 180.9 389.2 48zM364.4 421.8h39.1L151.1 88h-42L364.4 421.8z\"><\/path><\/svg><\/span><\/span><\/span><\/div>\n\n\n\n<div class=\"wp-block-uagb-social-share-child uagb-ss-repeater uagb-ss__wrapper uagb-block-1d136f14\"><span class=\"uagb-ss__link\" data-href=\"https:\/\/www.linkedin.com\/shareArticle?url=\" tabindex=\"0\" role=\"button\" aria-label=\"linkedin\"><span class=\"uagb-ss__source-wrap\"><span class=\"uagb-ss__source-icon\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" viewBox=\"0 0 448 512\"><path d=\"M416 32H31.9C14.3 32 0 46.5 0 64.3v383.4C0 465.5 14.3 480 31.9 480H416c17.6 0 32-14.5 32-32.3V64.3c0-17.8-14.4-32.3-32-32.3zM135.4 416H69V202.2h66.5V416zm-33.2-243c-21.3 0-38.5-17.3-38.5-38.5S80.9 96 102.2 96c21.2 0 38.5 17.3 38.5 38.5 0 21.3-17.2 38.5-38.5 38.5zm282.1 243h-66.4V312c0-24.8-.5-56.7-34.5-56.7-34.6 0-39.9 27-39.9 54.9V416h-66.4V202.2h63.7v29.2h.9c8.9-16.8 30.6-34.5 62.9-34.5 67.2 0 79.7 44.3 79.7 101.9V416z\"><\/path><\/svg><\/span><\/span><\/span><\/div>\n<\/div>\n<\/div>\n<\/div><\/div>\n\n\n\n<p class=\"wp-block-paragraph\">For 25 years, scientists have known that cells rely on a mechanism called RNA interference to control which genes get expressed \u2014 but the step-by-step machinery behind that process remained frustratingly opaque. Now, a team of researchers at The Ohio State University has produced the first detailed account of how a specific protein orchestrates the assembly of the complex that carries out this vital regulatory job.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The study, <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1097276526002832?via%3Dihub\" target=\"_blank\" rel=\"noopener\" title=\"\">published<\/a> May 26, in the journal <em>Molecular Cell<\/em>, focuses on a protein called Argonaute2 and its role in converting a precursor complex into a mature RNA-induced silencing complex, known as a RISC. It is RISCs that actually perform the work of suppressing gene expression inside cells.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Why RNA Interference Matters<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">RNA interference, or RNAi, is a natural process in which small RNA molecules prevent certain genes from producing proteins. Since its discovery in the late 1990s \u2014 work that earned a Nobel Prize \u2014 researchers have been racing to harness it as a therapeutic tool. The idea: design synthetic RNA molecules that slip into a cell and instruct it to silence a disease-causing gene. That potential has fueled billions of dollars in pharmaceutical investment, but a fundamental gap in understanding has held back progress.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Senior author Kotaro Nakanishi, a professor of chemistry and biochemistry at Ohio State, described the gap bluntly. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cThis mechanism has been a black box for a quarter century, since the discovery of RNA interference,\u201d Nakanishi said in a news release. \u201cVisualizing the mechanism is very important \u2013 pharmaceutical companies may appreciate our 3D structures because they can optimize or design a new drug based on them.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">How the Study Was Conducted<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Nakanishi&#8217;s team used two complementary approaches: biochemical assays and cryogenic-electron microscopy, a cutting-edge imaging technique that can resolve molecular structures in extraordinary detail. Using Argonaute2 as their model, the researchers began by incubating the human protein with a specific type of RNA segment called a small interfering RNA, or siRNA, duplex \u2014 essentially a paired double strand of RNA.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">What they observed unfolded in four distinct stages. First, Argonaute2 loads the double-stranded RNA. Second, it selects one of the two strands to act as a guide while flagging the other \u2014 the so-called passenger strand \u2014 for removal. Third, it unwinds the duplex. Finally, in what may be the study&#8217;s most striking finding, it ejects the passenger strand with unexpected help.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">A Surprising Co-Star: The Messenger RNA<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">The final step held a genuine surprise. Scientists had long assumed that messenger RNAs, or mRNAs, played only a passive role in RNA interference \u2014 serving as targets to be silenced, not active participants in the silencing machinery. But the Ohio State team found that mRNA molecules help cast off the passenger strand during the final assembly step. The researchers dubbed this stage TAPE, for target-assisted passenger ejection.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In their paper, the authors wrote that their results &#8220;suggest that mRNAs can also bind precursor RISCs and facilitate passenger removal during RISC maturation&#8221; \u2014 a departure from how the field has traditionally thought about mRNA&#8217;s role in this pathway. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Nakanishi offered an intuitive explanation for why this might make sense: if a cell is already targeting abundant mRNAs, it is efficient for those same molecules to lend a hand in completing the silencing complex.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Implications for Gene-Silencing Therapies<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">The practical stakes are substantial. Therapeutic siRNAs are already being explored as treatments for conditions ranging from rare genetic disorders to high cholesterol, and the field is expanding rapidly. But without understanding how RISCs are actually formed, researchers have been working with an incomplete blueprint.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">&#8220;Researchers and pharmaceutical companies have been using siRNAs as a potential therapy to shut down gene expression and study the role of the protein of interest. However, nobody knows how RISCs are formed,&#8221; Nakanishi added. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">With this structural map now in hand, his lab argues it becomes possible to rationally design or optimize siRNA molecules rather than relying on trial and error.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The findings may also benefit a newer class of molecules called cityRNAs \u2014 cleavage-inducing tiny RNAs \u2014 which are designed to override natural cellular processes and direct a targeted silencing response against genes linked to specific diseases. Nakanishi is a co-founder and scientific adviser of City Therapeutics, Inc., which works with this technology.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">What Comes Next<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Argonaute2 is just one of four proteins in the Argonaute family involved in RNA interference. While the team&#8217;s biochemical data suggest all four behave similarly during RISC assembly, Nakanishi&#8217;s lab is now conducting parallel experiments to confirm how the other three proteins carry out the same process. That work could further refine the structural picture and expand its applications.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Co-authors on the study included Huaqun Zhang, Vishal Annasaheb Adhav, Audrey Kehling, Andrew Savidge and Zhangfei Shen from Ohio State, as well as Tianmin Fu from the University of Massachusetts Chan Medical School. Cryo-EM imaging support was provided by Giovanna Grandinetti and Yohie Narui of Ohio State&#8217;s Center for Electron Microscopy and Analysis.<\/p>\n\n\n\n<div style=\"height:6px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Source: <\/strong><a href=\"https:\/\/news.osu.edu\/unsealing-cells-black-box-strategy-to-regulate-gene-activation\/\" target=\"_blank\" rel=\"noopener\" title=\"\">The Ohio State University<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>A new Ohio State University study is the first to detail how a key protein builds the molecular complex responsible for RNA interference \u2014 a gene-regulating process discovered over two decades ago. The findings could reshape how scientists design gene-silencing therapies for disease.<\/p>\n","protected":false},"author":3,"featured_media":37617,"comment_status":"open","ping_status":"open","sticky":false,"template":"single-no-separators","format":"standard","meta":{"_acf_changed":false,"_uag_custom_page_level_css":"","_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[25],"tags":[2034,2397,2395,2396,894,908,57,2394,585],"class_list":["post-37618","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","tag-biochemistry","tag-city-therapeutics-inc","tag-gene-expression","tag-gene-therapy","tag-molecular-biology","tag-nih","tag-ohio-state-university","tag-rna-interference","tag-university-of-massachusetts-chan-medical-school"],"acf":[],"aioseo_notices":[],"uagb_featured_image_src":{"full":["https:\/\/www.tun.com\/home\/wp-content\/uploads\/2026\/05\/ohio-state-unlocks-25-year-mystery-of-rna-interference-mecha.png",1536,1024,false],"thumbnail":["https:\/\/www.tun.com\/home\/wp-content\/uploads\/2026\/05\/ohio-state-unlocks-25-year-mystery-of-rna-interference-mecha-150x150.png",150,150,true],"medium":["https:\/\/www.tun.com\/home\/wp-content\/uploads\/2026\/05\/ohio-state-unlocks-25-year-mystery-of-rna-interference-mecha-300x200.png",300,200,true],"medium_large":["https:\/\/www.tun.com\/home\/wp-content\/uploads\/2026\/05\/ohio-state-unlocks-25-year-mystery-of-rna-interference-mecha-768x512.png",768,512,true],"large":["https:\/\/www.tun.com\/home\/wp-content\/uploads\/2026\/05\/ohio-state-unlocks-25-year-mystery-of-rna-interference-mecha-1024x683.png",1024,683,true],"1536x1536":["https:\/\/www.tun.com\/home\/wp-content\/uploads\/2026\/05\/ohio-state-unlocks-25-year-mystery-of-rna-interference-mecha.png",1536,1024,false],"2048x2048":["https:\/\/www.tun.com\/home\/wp-content\/uploads\/2026\/05\/ohio-state-unlocks-25-year-mystery-of-rna-interference-mecha.png",1536,1024,false]},"uagb_author_info":{"display_name":"The University Network","author_link":"https:\/\/www.tun.com\/home\/author\/funky_junkie\/"},"uagb_comment_info":0,"uagb_excerpt":"A new Ohio State University study is the first to detail how a key protein builds the molecular complex responsible for RNA interference \u2014 a gene-regulating process discovered over two decades ago. The findings could reshape how scientists design gene-silencing therapies for disease.","_links":{"self":[{"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/posts\/37618","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/comments?post=37618"}],"version-history":[{"count":8,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/posts\/37618\/revisions"}],"predecessor-version":[{"id":37664,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/posts\/37618\/revisions\/37664"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/media\/37617"}],"wp:attachment":[{"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/media?parent=37618"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/categories?post=37618"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/tags?post=37618"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}