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Most mutations adversely affect HERG channel assembly and trafficking. Why the channel is so vulnerable to missense mutations is not well understood. Since nothing is known of how mRNA structural elements factor in channel processing, we synthesized a codon\u2010modified HERG cDNA (HERG\u2010CM) where the codons were synonymously changed to reduce GC content, secondary structure, and rare codon usage. HERG\u2010CM produced typical I\n                    <jats:sub>Kr<\/jats:sub>\n                    \u2010like currents; however, channel synthesis and processing were markedly different. Translation efficiency was reduced for HERG\u2010CM, as determined by heterologous expression,\n                    <jats:italic>in vitro<\/jats:italic>\n                    translation, and polysomal profiling. Trafficking efficiency to the cell surface was greatly enhanced, as assayed by immunofluorescence, subcellular fractionation, and surface labeling. Chimeras of HERG\u2010NT\/CM indicated that trafficking efficiency was largely dependent on 5' sequences, while translation efficiency involved multiple areas. These results suggest that HERG translation and trafficking rates are independently governed by noncoding information in various regions of the mRNA molecule. Noncoding information embedded within the mRNA may play a role in the pathogenesis of hereditary arrhythmia syndromes and could provide an avenue for targeted therapeutics.\u2014Sroubek, J., Krishnan, Y., McDonald, T V. Sequence\u2010 and structure\u2010specific elements of HERG mRNA determine channel synthesis and trafficking efficiency. FASEB J. 27, 3039\u20133053 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-227009","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T04:31:36Z","timestamp":1366691496000},"page":"3039-3053","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sequence and structure\u2010specific elements of HERG mRNA determine channel synthesis and trafficking efficiency"],"prefix":"10.1096","volume":"27","author":[{"given":"Jakub","family":"Sroubek","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamini","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas V.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology Albert Einstein College of Medicine Bronx New York USA"},{"name":"Department of Medicine Wilf Family Cardiovascular Research Center Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,4,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25537"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.02.068"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.8.3438"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90340-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.570200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.012914"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.08.002"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.01.006"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2009.01.008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2005.01583.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.08.621"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.549071"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.180223197"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg055"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1135308"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.154575"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh273"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305787200"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.043"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.269993"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.292"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg563"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)02024-2"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.11.1427"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-008-9118-4"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/40882"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0346-04.2004"},{"key":"e_1_2_7_29_1","first-page":"36","article-title":"Image Processing with ImageJ","volume":"11","author":"Abramoff M. 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