{"id":465,"date":"2023-03-17T14:01:01","date_gmt":"2023-03-17T14:01:01","guid":{"rendered":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/?post_type=chapter&#038;p=465"},"modified":"2023-04-07T10:25:11","modified_gmt":"2023-04-07T10:25:11","slug":"eukaryotic-translation-initiation","status":"publish","type":"chapter","link":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/chapter\/eukaryotic-translation-initiation\/","title":{"raw":"Eukaryotic Translation-Initiation","rendered":"Eukaryotic Translation-Initiation"},"content":{"raw":"<div>The process of initiation can be grouped in to 4 main headings as<\/div>\r\n<ul>\r\n \t<li>Ribosome dissociation in to 40 S and 60 S<\/li>\r\n \t<li>Ternary complex\u00a0 called pre initiation complex formation \u2013 initiator t RNA +GTP+ eIF2+40S ribosomal subunit<\/li>\r\n \t<li>mRNA binding to preinitiation complex<\/li>\r\n \t<li>60S ribosomal subunit binding to the complex<\/li>\r\n<\/ul>\r\n<h1>The steps in the process of initiation<\/h1>\r\n<div>The steps can be summarized as :<\/div>\r\n<ul>\r\n \t<li>GTP binds to eIF2- Binary complex<\/li>\r\n \t<li>eIF2 composed of 3 subunits \u2013 \u03b1, \u03b2 and \u03b3.<\/li>\r\n \t<li>Binary complex binding to initiator t RNA<\/li>\r\n \t<li>Binding of 40S ribosomal subunit<\/li>\r\n \t<li>Ternary complex \u2013<strong> called 43S preinitiation complex<\/strong>.\u00a0 This complex is stabilized by earlier\u00a0 association of eIF3 and eIF1 to the 40S subunit<\/li>\r\n \t<li>Eukaryotes does not require the Shine-Dalgarno sequence rather the eukaryotic initiation complex recognizes the 7-methylguanosine cap at the 5' end of the mRNA.<\/li>\r\n \t<li>Cap structure of mRNA is bound by eIFs prior to pre initiation complex formation. <strong>Cap binding accomplished by e IF -4F<\/strong>\r\n<div>This factor is a complex of 3 proteins\u00a0 namely\u00a0 <strong>eIF-4E, A and G\u00a0<\/strong><\/div>\r\n<div><strong>eIF-4E\u00a0<\/strong>\u00a0\u00a0 -\u00a0\u00a0\u00a0 24 KDa protein, recognizes and binds cap structure<\/div>\r\n<div><strong>eIF-4A\u00a0\u00a0<\/strong> -\u00a0\u00a0\u00a0 46 KDa protein, binds and hydrolyses ATP , exhibits RNA helicase activity, resolves RNA secondary structures.<\/div>\r\n<div><strong>eIF- 4G<\/strong> \u00a0\u00a0 - helps in the binding of mRNA to 43S preinitiation complex<\/div><\/li>\r\n \t<li>The cap-binding protein (CBP) and\u00a0 IFs assist the movement of the ribosome to the 5' cap. Once at the cap, the initiation complex moves\u00a0 along the mRNA in the 5' to 3' direction, searching for the AUG start codon.<\/li>\r\n \t<li>Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case.<\/li>\r\n \t<li>According to<span>\u00a0<\/span><strong><span data-type=\"term\" id=\"term-00006\">Kozak\u2019s rules<\/span><\/strong>, the nucleotides around the AUG indicate whether it is the correct start codon<em>. <strong>[pb_glossary id=\"938\"]Kozak\u2019s rules[\/pb_glossary] state that the following consensus sequence must appear around the AUG of vertebrate genes: 5'-gccRccAUGG-3'. The R (for purine) indicates a site that can be either A or G, but cannot be C or U. Sequences closer to this consensus show higher efficiency of translation. <\/strong><\/em><\/li>\r\n \t<li><span style=\"font-size: 1em\">e IF-5 binds to preinitiation complex. This is followed by the b<\/span>inding of initiator t RNA \u2013 met \u2013tRNA met \u00a0\u00a0to the AUG codon of mRNA ( process helped by eIF-1)<\/li>\r\n \t<li>This is followed by the binding of 60S subunit and results in the formation of 80S complex.<\/li>\r\n \t<li>Association of 60S requires e IF-5.Energy for the binding dervied by GTP hydrolysis \u2013 bound to eIF-2.<\/li>\r\n \t<li>\r\n<h1>eIF-2 cycle<\/h1>\r\n<\/li>\r\n<\/ul>\r\n<div>\u2022GDP bound form of eIF-2\u00a0 binds to e IF-2B<\/div>\r\n<div>\u2022eIF-2B stimulates exchange of GTP for GDP( therefore called GEF-Guanine nucleotide exchange factor).<\/div>\r\n<div>\u2022eIF-2B dissociate from eIF-2<\/div>\r\n<div><img src=\"http:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-content\/uploads\/sites\/17\/2023\/03\/Eukaryotic-translationinitiation.png\" alt=\"Picture depicting sequence of event in eukaryotic translation\" width=\"1014\" height=\"899\" class=\"aligncenter size-full wp-image-491\" \/><\/div>\r\n<div><\/div>\r\n<div style=\"text-align: center\"><span style=\"color: #993366;background-color: #ffffff\"><a href=\"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/4\/45\/Eukaryotic_initiation.png\" target=\"_blank\" rel=\"noopener\" style=\"color: #993366;background-color: #ffffff\">\"Eukaryotic Translation Initiation\"<\/a>\u00a0by\u00a0<a style=\"color: #993366;background-color: #ffffff\">Webridge via wikemedia<\/a><a style=\"color: #993366;background-color: #ffffff\"><\/a><a style=\"color: #993366;background-color: #ffffff\"><\/a>\u00a0is licensed under\u00a0<a href=\"http:\/\/creativecommons.org\/licenses\/by\/3.0\" target=\"_blank\" rel=\"noopener\" style=\"color: #993366;background-color: #ffffff\">CC BY 3.0<\/a><\/span><\/div>\r\n<div><\/div>\r\n<div><\/div>\r\n<div><\/div>\r\n<div><\/div>","rendered":"<div>The process of initiation can be grouped in to 4 main headings as<\/div>\n<ul>\n<li>Ribosome dissociation in to 40 S and 60 S<\/li>\n<li>Ternary complex\u00a0 called pre initiation complex formation \u2013 initiator t RNA +GTP+ eIF2+40S ribosomal subunit<\/li>\n<li>mRNA binding to preinitiation complex<\/li>\n<li>60S ribosomal subunit binding to the complex<\/li>\n<\/ul>\n<h1>The steps in the process of initiation<\/h1>\n<div>The steps can be summarized as :<\/div>\n<ul>\n<li>GTP binds to eIF2- Binary complex<\/li>\n<li>eIF2 composed of 3 subunits \u2013 \u03b1, \u03b2 and \u03b3.<\/li>\n<li>Binary complex binding to initiator t RNA<\/li>\n<li>Binding of 40S ribosomal subunit<\/li>\n<li>Ternary complex \u2013<strong> called 43S preinitiation complex<\/strong>.\u00a0 This complex is stabilized by earlier\u00a0 association of eIF3 and eIF1 to the 40S subunit<\/li>\n<li>Eukaryotes does not require the Shine-Dalgarno sequence rather the eukaryotic initiation complex recognizes the 7-methylguanosine cap at the 5&#8242; end of the mRNA.<\/li>\n<li>Cap structure of mRNA is bound by eIFs prior to pre initiation complex formation. <strong>Cap binding accomplished by e IF -4F<\/strong>\n<div>This factor is a complex of 3 proteins\u00a0 namely\u00a0 <strong>eIF-4E, A and G\u00a0<\/strong><\/div>\n<div><strong>eIF-4E\u00a0<\/strong>\u00a0\u00a0 &#8211;\u00a0\u00a0\u00a0 24 KDa protein, recognizes and binds cap structure<\/div>\n<div><strong>eIF-4A\u00a0\u00a0<\/strong> &#8211;\u00a0\u00a0\u00a0 46 KDa protein, binds and hydrolyses ATP , exhibits RNA helicase activity, resolves RNA secondary structures.<\/div>\n<div><strong>eIF- 4G<\/strong> \u00a0\u00a0 &#8211; helps in the binding of mRNA to 43S preinitiation complex<\/div>\n<\/li>\n<li>The cap-binding protein (CBP) and\u00a0 IFs assist the movement of the ribosome to the 5&#8242; cap. Once at the cap, the initiation complex moves\u00a0 along the mRNA in the 5&#8242; to 3&#8242; direction, searching for the AUG start codon.<\/li>\n<li>Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case.<\/li>\n<li>According to<span>\u00a0<\/span><strong><span data-type=\"term\" id=\"term-00006\">Kozak\u2019s rules<\/span><\/strong>, the nucleotides around the AUG indicate whether it is the correct start codon<em>. <strong><a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_465_938\">Kozak\u2019s rules<\/a> state that the following consensus sequence must appear around the AUG of vertebrate genes: 5&#8242;-gccRccAUGG-3&#8242;. The R (for purine) indicates a site that can be either A or G, but cannot be C or U. Sequences closer to this consensus show higher efficiency of translation. <\/strong><\/em><\/li>\n<li><span style=\"font-size: 1em\">e IF-5 binds to preinitiation complex. This is followed by the b<\/span>inding of initiator t RNA \u2013 met \u2013tRNA met \u00a0\u00a0to the AUG codon of mRNA ( process helped by eIF-1)<\/li>\n<li>This is followed by the binding of 60S subunit and results in the formation of 80S complex.<\/li>\n<li>Association of 60S requires e IF-5.Energy for the binding dervied by GTP hydrolysis \u2013 bound to eIF-2.<\/li>\n<li>\n<h1>eIF-2 cycle<\/h1>\n<\/li>\n<\/ul>\n<div>\u2022GDP bound form of eIF-2\u00a0 binds to e IF-2B<\/div>\n<div>\u2022eIF-2B stimulates exchange of GTP for GDP( therefore called GEF-Guanine nucleotide exchange factor).<\/div>\n<div>\u2022eIF-2B dissociate from eIF-2<\/div>\n<div><img decoding=\"async\" src=\"http:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-content\/uploads\/sites\/17\/2023\/03\/Eukaryotic-translationinitiation.png\" alt=\"Picture depicting sequence of event in eukaryotic translation\" width=\"1014\" height=\"899\" class=\"aligncenter size-full wp-image-491\" srcset=\"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-content\/uploads\/sites\/17\/2023\/03\/Eukaryotic-translationinitiation.png 1014w, https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-content\/uploads\/sites\/17\/2023\/03\/Eukaryotic-translationinitiation-300x266.png 300w, https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-content\/uploads\/sites\/17\/2023\/03\/Eukaryotic-translationinitiation-768x681.png 768w, https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-content\/uploads\/sites\/17\/2023\/03\/Eukaryotic-translationinitiation-65x58.png 65w, https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-content\/uploads\/sites\/17\/2023\/03\/Eukaryotic-translationinitiation-225x199.png 225w, https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-content\/uploads\/sites\/17\/2023\/03\/Eukaryotic-translationinitiation-350x310.png 350w\" sizes=\"(max-width: 1014px) 100vw, 1014px\" \/><\/div>\n<div><\/div>\n<div style=\"text-align: center\"><span style=\"color: #993366;background-color: #ffffff\"><a href=\"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/4\/45\/Eukaryotic_initiation.png\" target=\"_blank\" rel=\"noopener\" style=\"color: #993366;background-color: #ffffff\">&#8220;Eukaryotic Translation Initiation&#8221;<\/a>\u00a0by\u00a0<a style=\"color: #993366;background-color: #ffffff\">Webridge via wikemedia<\/a><a style=\"color: #993366;background-color: #ffffff\"><\/a><a style=\"color: #993366;background-color: #ffffff\"><\/a>\u00a0is licensed under\u00a0<a href=\"http:\/\/creativecommons.org\/licenses\/by\/3.0\" target=\"_blank\" rel=\"noopener\" style=\"color: #993366;background-color: #ffffff\">CC BY 3.0<\/a><\/span><\/div>\n<div><\/div>\n<div><\/div>\n<div><\/div>\n<div><\/div>\n<div class=\"glossary\"><span class=\"screen-reader-text\" id=\"definition\">definition<\/span><template id=\"term_465_938\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_465_938\"><div tabindex=\"-1\"><p>State that the consensus sequence 5' -gccRccAUCC-3' must appear around AUG of vertebrate genes. Sequences closer to this consensus show higher efficiency of translation<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><\/div>","protected":false},"author":5,"menu_order":20,"template":"","meta":{"om_disable_all_campaigns":false,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"_uf_show_specific_survey":0,"_uf_disable_surveys":false,"pb_show_title":"on","pb_short_title":"Eukaryotic Translation-Initiation","pb_subtitle":"Eukaryotic Translation-Initiation","pb_authors":["dr-v-malathi"],"pb_section_license":"cc-by-sa"},"chapter-type":[],"contributor":[61],"license":[54],"class_list":["post-465","chapter","type-chapter","status-publish","hentry","contributor-dr-v-malathi","license-cc-by-sa"],"aioseo_notices":[],"part":3,"_links":{"self":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters\/465","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/users\/5"}],"version-history":[{"count":24,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters\/465\/revisions"}],"predecessor-version":[{"id":1005,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters\/465\/revisions\/1005"}],"part":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/parts\/3"}],"metadata":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters\/465\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/media?parent=465"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapter-type?post=465"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/contributor?post=465"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/license?post=465"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}