{"id":6160,"date":"2026-08-20T13:34:55","date_gmt":"2026-08-20T06:34:55","guid":{"rendered":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/?p=6160"},"modified":"2026-08-20T13:39:18","modified_gmt":"2026-08-20T06:39:18","slug":"antisense-oligonucleotide-induction-of-the-hnrnpa1b-isoform-affects-pre-mrna-splicing-of-smn2-in-sma-type-i-fibroblasts","status":"publish","type":"post","link":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/antisense-oligonucleotide-induction-of-the-hnrnpa1b-isoform-affects-pre-mrna-splicing-of-smn2-in-sma-type-i-fibroblasts\/","title":{"rendered":"Antisense Oligonucleotide Induction of the hnRNPA1b Isoform Affects Pre-mRNA Splicing of SMN2 in SMA Type I Fibroblasts"},"content":{"rendered":"<p><strong>Jarichad Toosaranont<\/strong>, Sukanya Ruschadaariyachat, Warasinee Mujchariyakul, Jantarika Kumar Arora, <strong>Varodom Charoensawan<\/strong>, <strong>Bhoom Suktitipat<\/strong>, Thomas N Palmer, Sue Fletcher, Steve D Wilton, <strong>Chalermchai Mitrpant<\/strong><\/p>\n<h2 class=\"title\">Abstract<\/h2>\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<div class=\"title\">\n<p>Spinal muscular atrophy (SMA) is a severe, debilitating neuromuscular condition characterised by loss of motor neurons and progressive muscle wasting. SMA is caused by a loss of expression of SMN1 that encodes the survival motor neuron (SMN) protein necessary for the survival of motor neurons. Restoration of SMN expression through increased inclusion of SMN2 exon 7 is known to ameliorate symptoms in SMA patients. As a consequence, regulation of pre-mRNA splicing of SMN2 could provide a potential molecular therapy for SMA. In this study, we explored if splice switching antisense oligonucleotides could redirect the splicing repressor hnRNPA1 to the hnRNPA1b isoform and restore SMN expression in fibroblasts from a type I SMA patient. Antisense oligonucleotides (AOs) were designed to promote exon 7b retention in the mature mRNA and induce the hnRNPA1b isoform. RT-PCR and western blot analysis were used to assess and monitor the efficiency of different AO combinations. A combination of AOs targeting multiple silencing motifs in hnRNPA1 pre-mRNA led to robust hnRNPA1b induction, which, in turn, significantly increased expression of full-length SMN (FL-SMN) protein. A combination of PMOs targeting the same motifs also strongly induced hnRNPA1b isoform, but surprisingly SMN2 exon 5 skipping was detected, and the PMO cocktail did not lead to a significant increase in expression of FL-SMN protein. We further performed RNA sequencing to assess the genome-wide effects of hnRNPA1b induction. Some 3244 genes were differentially expressed between the hnRNPA1b-induced and untreated SMA fibroblasts, which are functionally enriched in cell cycle and chromosome segregation processes. RT-PCR analysis demonstrated that expression of the master regulator of these enrichment pathways, MYBL2 and FOXM1B, were reduced in response to PMO treatment. These findings suggested that induction of hnRNPA1b can promote SMN protein expression, but not at sufficient levels to be clinically relevant.<\/p>\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/35409296\/\">https:\/\/pubmed.ncbi.nlm.nih.gov\/35409296\/<\/a><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Jarichad Toosaranont, Sukanya Ruschadaariyachat, Warasi [&#8230;]\n","protected":false},"author":6,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-6160","post","type-post","status-publish","format-standard","hentry","category-3"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Antisense Oligonucleotide Induction of the hnRNPA1b Isoform Affects Pre-mRNA Splicing of SMN2 in SMA Type I Fibroblasts - 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\u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25\" \/>\n<meta property=\"og:description\" content=\"Jarichad Toosaranont, Sukanya Ruschadaariyachat, Warasi [...]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/antisense-oligonucleotide-induction-of-the-hnrnpa1b-isoform-affects-pre-mrna-splicing-of-smn2-in-sma-type-i-fibroblasts\/\" \/>\n<meta property=\"og:site_name\" content=\"\u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/SIBBprogram\/\" \/>\n<meta property=\"article:published_time\" content=\"2026-08-20T06:34:55+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-08-20T06:39:18+00:00\" \/>\n<meta name=\"author\" content=\"Poorintra Sakuna\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Poorintra Sakuna\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 \u0e19\u0e32\u0e17\u0e35\" \/>\n<script type=\"application\/ld+json\" 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