{"id":327,"date":"2019-07-17T19:01:18","date_gmt":"2019-07-17T19:01:18","guid":{"rendered":"https:\/\/labs.bio.cmu.edu\/mcmanus\/?page_id=327"},"modified":"2025-05-26T18:07:59","modified_gmt":"2025-05-26T18:07:59","slug":"translation-regulation-evolution","status":"publish","type":"page","link":"https:\/\/labs.bio.cmu.edu\/mcmanus\/research\/translation-regulation-evolution\/","title":{"rendered":"Upstream Open Reading Frames (uORFs)"},"content":{"rendered":"

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Upstream Open Reading Frames (uORFs)<\/h1><\/div>\n\t\t\t<\/div>
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Changes in gene expression have significant impacts on biological phenotypes, including human disease. These changes can occur in all gene expression processes, including mRNA transcription, alternative splicing, translation into protein, and mRNA and protein turnover. The regulation of these processes involves complex networks comprised of\u00a0cis<\/em>-acting DNA and RNA sequence elements, and\u00a0trans<\/em>-acting factors. Over the past decade it has become increasingly clear that changes in both types of network components have contributed to widespread differences in mRNA abundance, both among and between species. However, species differences in mRNA abundance may not accurately reflect differences in protein expression and comparatively little is known regarding the evolution of post-transcriptional gene regulatory processes. \u00a0We are currently using both laboratory and computational based methods to investigate upstream open reading frames (uORFs), and how they affect translation regulation in yeast and human cells. We are also particularly interested in the structure and function of conserved 5'UTRs.<\/p><\/div>\n\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\t\n\t\t\t\t\n\t\t\t<\/div>

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Selected Publications<\/h3><\/div>\n\t\t\t<\/div>
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Akritava, C, May GE, McManus CJ. (2025) Deciphering the landscape of cis-acting sequences in natural yeast Transcript Leaders. <\/em>Nucleic Acids Research<\/em><\/a><\/p>\n

May GE, Akirtava C, Agar-Johnson M, Micic J, Woolford J, McManus J.<\/strong> (2023) Unraveling the influences of sequence and position on yeast uORF activity using massively parallel reporter systems and machine learning. eLife<\/em><\/a><\/p>\n

Akirtava C, May GE, McManus J.<\/strong> (2022) False-positive IRESes from Hoxa9 and other genes resulting from errors in mammalian 5\u2032 UTR annotations. PNAS<\/a>. <\/em><\/p>\n

May G, McManus J. <\/strong>(2022) Multiplexed Analysis of Human uORF Regulatory Functions During the ISR Using PoLib-Seq. Methods Mol Biol.<\/em><\/a><\/p>\n

May G, McManus J<\/strong>. (2022)\u00a0 High-Throughput Quantitation of Yeast uORF Regulatory Impacts Using FACS-uORF. Methods Mol Biol.<\/em><\/a><\/p>\n

Spealman P, Naik A, McManus J.<\/strong> (2021) uORF-seqr: A Machine Learning-Based Approach to the Identification of Upstream Open Reading Frames in Yeast. Methods in Mol. Biol.<\/a><\/em><\/p>\n

Lin Y, May G, Kready H, Nazzaro L, Mao M, Spealman P, Creeger Y, McManus CJ<\/strong>. (2019) Impacts of uORF codon identity and position on translation regulation. Nucleic Acids Research<\/a><\/em><\/p>\n

Spealman P, Naik A, May G, Kuersten S, Freebert L, Murphy R, McManus J.<\/strong> (2017) Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data. Genome Research<\/em><\/a><\/p>\n

McManus CJ<\/strong>, May G, Spealman P, Shteyman A. (2013) Ribosome profiling reveals post-transcriptional buffering of divergent gene expression in yeast.\u00a0Genome Research<\/a><\/em><\/p><\/div>\n\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\t\n\t\t\t\t\n\t\t\t<\/div><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":21,"featured_media":0,"parent":8,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"

<\/header>\r\n
\r\n\r\n\"\"\r\n\r\nChanges in gene expression have significant impacts on biological phenotypes, including human disease. These changes can occur in all gene expression processes, including mRNA transcription, alternative splicing, translation into protein, and mRNA and protein turnover. The regulation of these processes involves complex networks comprised of\u00a0cis<\/em>-acting DNA and RNA sequence elements, and\u00a0trans<\/em>-acting factors. Over the past decade it has become increasingly clear that changes in both types of network components have contributed to widespread differences in mRNA abundance, both among and between species. However, species differences in mRNA abundance may not accurately reflect differences in protein expression and comparatively little is known regarding the evolution of post-transcriptional gene regulatory processes. \u00a0We are currently using both laboratory and computational based methods to investigate upstream open reading frames (uORFs), and how they affect translation regulation in yeast and human cells. We are also particularly interested in the structure and function of conserved 5'UTRs.\r\n\r\n<\/div>\r\n

<\/h4>\r\n

Selected Publications<\/h4>\r\nAkritava, C, May GE, McManus CJ. (2025) Deciphering the landscape of cis-acting sequences in natural yeast Transcript Leaders. Accepted to <\/em>Nucleic Acids Research<\/em><\/a>\r\n\r\nMay GE, Akirtava C, Agar-Johnson M, Micic J, Woolford J, McManus J.<\/strong> (2023) Unraveling the influences of sequence and position on yeast uORF activity using massively parallel reporter systems and machine learning. eLife<\/em><\/a>\r\n\r\nAkirtava C, May GE, McManus J.<\/strong> (2022) False-positive IRESes from Hoxa9 and other genes resulting from errors in mammalian 5\u2032 UTR annotations. PNAS<\/a>. <\/em>\r\n\r\nMay G, McManus J. <\/strong>(2022) Multiplexed Analysis of Human uORF Regulatory Functions During the ISR Using PoLib-Seq. Methods Mol Biol.<\/em><\/a>\r\n\r\nMay G, McManus J<\/strong>. (2022)\u00a0 High-Throughput Quantitation of Yeast uORF Regulatory Impacts Using FACS-uORF. Methods Mol Biol.<\/em><\/a>\r\n\r\nSpealman P, Naik A, McManus J.<\/strong> (2021) uORF-seqr: A Machine Learning-Based Approach to the Identification of Upstream Open Reading Frames in Yeast. Methods in Mol. Biol<\/a><\/em>\r\n\r\nLin Y, May G, Kready H, Nazzaro L, Mao M, Spealman P, Creeger Y, McManus CJ<\/strong>. (2019) Impacts of uORF codon identity and position on translation regulation. Nucleic Acids Research<\/a><\/em>\r\n\r\nSpealman P, Naik A, May G, Kuersten S, Freebert L, Murphy R, McManus J.<\/strong> (2017) Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data. Genome Research<\/em><\/a>.\r\n\r\nMcManus CJ<\/strong>, May G, Spealman P, Shteyman A. (2013) Ribosome profiling reveals post-transcriptional buffering of divergent gene expression in yeast.\u00a0Genome Research<\/a><\/em>\r\n\r\n \r\n\r\n \r\n\r\n \r\n\r\n ","_et_gb_content_width":"","footnotes":""},"class_list":["post-327","page","type-page","status-publish","hentry"],"jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/ParKnc-5h","_links":{"self":[{"href":"https:\/\/labs.bio.cmu.edu\/mcmanus\/wp-json\/wp\/v2\/pages\/327","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.bio.cmu.edu\/mcmanus\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labs.bio.cmu.edu\/mcmanus\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labs.bio.cmu.edu\/mcmanus\/wp-json\/wp\/v2\/users\/21"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.bio.cmu.edu\/mcmanus\/wp-json\/wp\/v2\/comments?post=327"}],"version-history":[{"count":19,"href":"https:\/\/labs.bio.cmu.edu\/mcmanus\/wp-json\/wp\/v2\/pages\/327\/revisions"}],"predecessor-version":[{"id":710,"href":"https:\/\/labs.bio.cmu.edu\/mcmanus\/wp-json\/wp\/v2\/pages\/327\/revisions\/710"}],"up":[{"embeddable":true,"href":"https:\/\/labs.bio.cmu.edu\/mcmanus\/wp-json\/wp\/v2\/pages\/8"}],"wp:attachment":[{"href":"https:\/\/labs.bio.cmu.edu\/mcmanus\/wp-json\/wp\/v2\/media?parent=327"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}