{"id":558269,"date":"2023-03-02T00:25:27","date_gmt":"2023-03-01T21:25:27","guid":{"rendered":"https:\/\/en.buradabiliyorum.com\/previously-unknown-mechanism-in-precision-rna-cleaving-by-dicer-enzyme-revealed\/"},"modified":"2023-03-02T00:25:27","modified_gmt":"2023-03-01T21:25:27","slug":"previously-unknown-mechanism-in-precision-rna-cleaving-by-dicer-enzyme-revealed","status":"publish","type":"post","link":"https:\/\/buradabiliyorum.com\/en\/previously-unknown-mechanism-in-precision-rna-cleaving-by-dicer-enzyme-revealed\/","title":{"rendered":"#Previously unknown mechanism in precision RNA cleaving by Dicer enzyme revealed"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_85 counter-hierarchy ez-toc-counter ez-toc-custom ez-toc-container-direction\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Table of Contents<\/p>\n<label for=\"ez-toc-cssicon-toggle-item-6a368bda7960f\" class=\"ez-toc-cssicon-toggle-label\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #dd3333;color:#dd3333\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #dd3333;color:#dd3333\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/label><input type=\"checkbox\"  id=\"ez-toc-cssicon-toggle-item-6a368bda7960f\" checked aria-label=\"Toggle\" \/><nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-1'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/buradabiliyorum.com\/en\/previously-unknown-mechanism-in-precision-rna-cleaving-by-dicer-enzyme-revealed\/#%E2%80%9CPreviously_unknown_mechanism_in_precision_RNA_cleaving_by_Dicer_enzyme_revealed%E2%80%9D\" >&#8220;Previously unknown mechanism in precision RNA cleaving by Dicer enzyme revealed&#8221;<\/a><\/li><\/ul><\/nav><\/div>\n<h1><span class=\"ez-toc-section\" id=\"%E2%80%9CPreviously_unknown_mechanism_in_precision_RNA_cleaving_by_Dicer_enzyme_revealed%E2%80%9D\"><\/span>&#8220;Previously unknown mechanism in precision RNA cleaving by Dicer enzyme revealed&#8221;<span class=\"ez-toc-section-end\"><\/span><\/h1>\n<div>\n<div class=\"article-gallery lightGallery\">\n<div data-thumb=\"https:\/\/scx1.b-cdn.net\/csz\/news\/tmb\/2023\/previously-unknown-mec-2.jpg\" data-src=\"https:\/\/scx2.b-cdn.net\/gfx\/news\/hires\/2023\/previously-unknown-mec-2.jpg\" data-sub-html=\"Purification of hDICER and the hDICER\u2013RNA complex. a, The sequence of pre-let-7a-1&lt;sup&gt;GYM&lt;\/sup&gt; used for structural determination. b, SDS\u2013PAGE of wild-type and mutant hDICER proteins. c, Size-exclusion chromatography of purified proteins. d, In vitro processing of pre-let-7a-1 by purified hDICER. e, Size-exclusion chromatography of the hDICER\u2013pre-let-7a-1&lt;sup&gt;GYM&lt;\/sup&gt; complex. f, SDS\u2013PAGE of the hDICER\u2013pre-let-7a-1&lt;sup&gt;GYM&lt;\/sup&gt; complex visualized by Coomassie blue staining. Protein concentration for each fraction was estimated by Bradford protein assay, and the same amount of protein was loaded for each fraction. g, Urea-PAGE of the hDICER\u2013pre-let-7a-1&lt;sup&gt;GYM&lt;\/sup&gt; complex visualized by SYBR gold staining. RNA concentration for each fraction was estimated by absorbance at 260 nm, and the same amount of RNA was loaded for each fraction. Credit: &lt;i&gt;Nature&lt;\/i&gt; (2023). DOI: 10.1038\/s41586-023-05723-3\">\n<figure class=\"article-img\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/scx1.b-cdn.net\/csz\/news\/800a\/2023\/previously-unknown-mec-2.jpg\" alt=\"Previously unknown mechanism in precision RNA cleaving by Dicer enzyme revealed\" title=\"Purification of hDICER and the hDICER\u2013RNA complex. a, The sequence of pre-let-7a-1 GYM  used for structural determination. b, SDS\u2013PAGE of wild-type and mutant hDICER proteins. c, Size-exclusion chromatography of purified proteins. d, In vitro processing of pre-let-7a-1 by purified hDICER. e, Size-exclusion chromatography of the hDICER\u2013pre-let-7a-1 GYM  complex. f, SDS\u2013PAGE of the hDICER\u2013pre-let-7a-1 GYM  complex visualized by Coomassie blue staining. Protein concentration for each fraction was estimated by Bradford protein assay, and the same amount of protein was loaded for each fraction. g, Urea-PAGE of the hDICER\u2013pre-let-7a-1 GYM  complex visualized by SYBR gold staining. RNA concentration for each fraction was estimated by absorbance at 260 nm, and the same amount of RNA was loaded for each fraction. Credit:  Nature  (2023). DOI: 10.1038\/s41586-023-05723-3\" width=\"800\" height=\"530\"\/><figcaption class=\"text-darken text-low-up text-truncate-js text-truncate mt-3\">\n                Purification of hDICER and the hDICER\u2013RNA complex. a, The sequence of pre-let-7a-1<sup>GYM<\/sup> used for structural determination. b, SDS\u2013PAGE of wild-type and mutant hDICER proteins. c, Size-exclusion chromatography of purified proteins. d, In vitro processing of pre-let-7a-1 by purified hDICER. e, Size-exclusion chromatography of the hDICER\u2013pre-let-7a-1<sup>GYM<\/sup> complex. f, SDS\u2013PAGE of the hDICER\u2013pre-let-7a-1<sup>GYM<\/sup> complex visualized by Coomassie blue staining. Protein concentration for each fraction was estimated by Bradford protein assay, and the same amount of protein was loaded for each fraction. g, Urea-PAGE of the hDICER\u2013pre-let-7a-1<sup>GYM<\/sup> complex visualized by SYBR gold staining. RNA concentration for each fraction was estimated by absorbance at 260 nm, and the same amount of RNA was loaded for each fraction. Credit: <i>Nature<\/i> (2023). DOI: 10.1038\/s41586-023-05723-3<br \/>\n            <\/figcaption><\/figure>\n<\/div>\n<\/div>\n<p>Researchers at the Center for RNA Research, Institute for Basic <a href=\"https:\/\/buradabiliyorum.com\/en\/category\/sciencee\/\" data-internallinksmanager029f6b8e52c=\"5\" title=\"Science\" target=\"_blank\" rel=\"noopener\">Science<\/a> (IBS), in Seoul, have published a study with critical new insights into the structure and function of the Dicer enzyme.  Dicer is an enzyme required for the biogenesis of miRNAs and small interfering RNAs (siRNAs), which in turn are drivers of RNA silencing and post-tran<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/download-scripts-themes-apps\/\" data-internallinksmanager029f6b8e52c=\"9\" title=\"Download Scripts &amp; Themes &amp; Apps\" target=\"_blank\" rel=\"noopener\">script<\/a>ional regulating of gene expression, one of the bodies&#8217; many checks on protein production.<\/p>\n<section class=\"article-banner first-banner ads-336x280\"><!-- \/4988204\/Phys_Story_InText_Box --><br \/>\n      <\/section>\n<p>RNA silencing requires efficient processing of double-stranded RNA into miRNAs and siRNAs by Dicer. As the name implies, Dicer takes the larger structure, double-stranded RNA, and cuts it into smaller functioning pieces. The specificity of Dicer&#8217;s processing has previously only been partially understood, and some of the dicing activity, while functional, needed to be explained.<\/p>\n<p>The study, &#8220;Sequence determinant of small RNA production by DICER,&#8221; has been published in the journal <i>Nature<\/i>.<\/p>\n<p>The current research revealed a deeply conserved cis-acting element, termed the &#8220;GYM motif,&#8221; near the cleavage site. This means that when Dicer cleaves precursor RNA molecules to produce miRNA, it can use landmarks (cis-regulatory elements) within the RNA to know precisely where to cut. This mechanism allows Dicer to override the previously identified mechanism of &#8220;ruler&#8221;-like counting from the 5\u2032 and 3\u2032 ends of pre-miRNA and solves the mystery around how some of the precision dicings take place.<\/p>\n<p>The study employed massively parallel assays with pre-miRNA variants and human Dicer enzyme (DICER1). The researchers selectively altered the GYM motif, assessed the modified Dicer enzyme&#8217;s ability to process double-stranded RNA, and found it to be &#8220;a strong determinant of DICER-<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/social-mediaa\/\" data-internallinksmanager029f6b8e52c=\"1\" title=\"Social Media\" target=\"_blank\" rel=\"noopener\">media<\/a>ted processing.&#8221; The intact GYM motif also improved RNA interference.<\/p>\n<figure class=\"mb-4\" itemscope=\"\" itemtype=\"http:\/\/schema.org\/VideoObject\"><meta itemprop=\"name\" content=\"Previously unknown mechanism in precision RNA cleaving by Dicer enzyme revealed\"\/><meta itemprop=\"url\" content=\"https:\/\/scx2.b-cdn.net\/gfx\/video\/2023\/previously-unknown-mec.mp4\"\/><meta itemprop=\"description\" content=\"Stem recognition by dsRBD and RIIID. The C-terminal dsRBD of DICER shows a large conformational change to accommodate dsRNA in the catalytic valley. Near the cleavage sites, this major groove of the RNA helix is expanded and sandwiched between dsRBD and RIIIDa. The mismatch of the GYM motif is recognized by R1855 of dsRBD. Credit:  Nature  (2023). DOI: 10.1038\/s41586-023-05723-3\"\/><meta itemprop=\"uploadDate\" content=\"2023-03-01T16:20:39-05:00\"\/><meta itemprop=\"thumbnailUrl\" content=\"https:\/\/scx1.b-cdn.net\/gfx\/video_tmb\/2023\/previously-unknown-mec.mp4.jpg\"\/><meta itemprop=\"contentUrl\" content=\"https:\/\/scx2.b-cdn.net\/gfx\/video\/2023\/previously-unknown-mec.mp4\"\/><video class=\"embed-responsive embed-responsive-16by9\" id=\"jwVID72943\" controls=\"\" poster=\"https:\/\/scx1.b-cdn.net\/gfx\/video_tmb\/2023\/previously-unknown-mec.mp4.jpg\"><source src=\"https:\/\/scx2.b-cdn.net\/gfx\/video\/2023\/previously-unknown-mec.mp4\" type=\"video\/mp4\"\/><\/video><figcaption class=\"text-darken text-low-up mt-4\" itemprop=\"caption\">Stem recognition by dsRBD and RIIID. The C-terminal dsRBD of DICER shows a large conformational change to accommodate dsRNA in the catalytic valley. Near the cleavage sites, this major groove of the RNA helix is expanded and sandwiched between dsRBD and RIIIDa. The mismatch of the GYM motif is recognized by R1855 of dsRBD. Credit: <i>Nature<\/i> (2023). DOI: 10.1038\/s41586-023-05723-3<\/figcaption><\/figure>\n<p>The analysis also found that a cancer-associated substitution in Dicer disrupts the recognition of the GYM motif. This discovery could be critically important for future investigations as certain cancers are correlated with increased or decreased Dicer levels, and the association is not currently understood.<\/p>\n<p>Together, the researchers state that their findings &#8220;&#8230;reveal an integral and conserved mechanism of substrate recognition by DICER and provide a framework to understand how DICER produces small RNAs for biological and therapeutic regulation.&#8221;<\/p>\n<div class=\"article-main__more p-4\">\n                                                                                        <strong>More information:<\/strong><br \/>\n                                                Young-Yoon Lee et al, Structure of the human DICER\u2013pre-miRNA complex in a dicing state, <i>Nature<\/i> (2023).  <a rel=\"nofollow noopener\" target=\"_blank\" data-doi=\"1\" href=\"https:\/\/dx.doi.org\/10.1038\/s41586-023-05723-3\">DOI: 10.1038\/s41586-023-05723-3<\/a><\/p><\/div>\n<p class=\"article-main__note mt-4\">\n                                                  \u00a9 2023 Science X Network<\/p>\n<p>                                        <!-- print only --><\/p>\n<div class=\"d-none d-print-block\">\n<p>                                                <strong>Citation<\/strong>:<br \/>\n                                                Previously unknown mechanism in precision RNA cleaving by Dicer enzyme revealed (2023, March 1)<br \/>\n                                                retrieved 1 March 2023<br \/>\n                                                from https:\/\/phys.org\/<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/news\/\" data-internallinksmanager029f6b8e52c=\"2\" title=\"News\" target=\"_blank\" rel=\"noopener\">news<\/a>\/2023-03-previously-unknown-mechanism-precision-rna.html<\/p>\n<p>                                             This document is subject to copyright. 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