How RNA structure dictates the usage of a critical exon of spinal muscular atrophy gene

Nilsen, 2010, Expansion of the eukaryotic proteome by alternative splicing, Nature, 463, 457, 10.1038/nature08909 Kelemen, 2013, Function of alternative splicing, Gene, 514, 1, 10.1016/j.gene.2012.07.083 Raj, 2015, Alternative splicing in the mammalian nervous system: recent insights into mechanisms and functional roles, Neuron, 87, 14, 10.1016/j.neuron.2015.05.004 Baralle, 2017, Alternative splicing as a regulator of development and tissue identity, Nat. Rev. Mol. Cell. Biol., 18, 437, 10.1038/nrm.2017.27 Chuang, 2018, Integrative transcriptome sequencing reveals extensive alternative trans-splicing and cis-backsplicing in human cells, Nucleic Acids Res., 46, 3671, 10.1093/nar/gky032 Deveson, 2017, The dimensions, dynamics, and relevance of the mammalian noncoding transcriptome, Trends Genet., 33, 464, 10.1016/j.tig.2017.04.004 Kristensen, 2018, Circular RNAs are abundantly expressed and upregulated during human epidermal stem cell differentiation, RNA Biol., 15, 280, 10.1080/15476286.2017.1409931 Singh, 2012, A multi-exon-skipping detection assay reveals surprising diversity of splice isoforms of spinal muscular atrophy genes, PLoS One, 7, 10.1371/journal.pone.0049595 Seo, 2016, Oxidative stress triggers body-wide skipping of multiple exons of the spinal muscular atrophy gene, PLoS One, 11, 10.1371/journal.pone.0154390 Seo, 2016, A novel human-specific splice isoform alters the critical C-terminus of survival motor neuron protein, Sci. Rep., 6, 778, 10.1038/srep30778 Ottesen, 2019, Human survival motor neuron genes generate a vast repertoire of circular RNAs, Nucleic Acids Res., 47, 2884, 10.1093/nar/gkz034 da Costa, 2017, The role of alternative splicing coupled to nonsense-mediated mRNA decay in human disease, Int. J. Biochem. Cell Biol., 91, 168, 10.1016/j.biocel.2017.07.013 Zheng, 2016, Alternative splicing and nonsense-mediated mRNA decay enforce neural specific gene expression, Int. J. Dev. Neurosci., 55, 102, 10.1016/j.ijdevneu.2016.03.003 Lee, 2015, Mechanisms and regulation of alternative pre-mRNA splicing, Annu. Rev. Biochem., 84, 291, 10.1146/annurev-biochem-060614-034316 Dvinge, 2018, Regulation of alternative mRNA splicing: old players and new perspectives, FEBS Lett., 592, 2987, 10.1002/1873-3468.13119 Martinez-Contreras, 2006, Intronic binding sites for hnRNP A/B and hnRNP F/H proteins stimulate pre-mRNA splicing, PLoS Biol., 4, 10.1371/journal.pbio.0040021 Wang, 2010, iCLIP predicts the dual splicing effects of TIA-RNA interactions, PLoS Biol., 8, 10.1371/journal.pbio.1000530 Singh, 2010, An antisense microwalk reveals critical role of an intronic position linked to a unique long-distance interaction in pre mRNA splicing, RNA, 16, 1167, 10.1261/rna.2154310 Erkelenz, 2013, Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms, RNA, 19, 96, 10.1261/rna.037044.112 Fu, 2014, Context-dependent control of alternative splicing by RNA-binding proteins, Nat. Rev. Genet., 15, 689, 10.1038/nrg3778 Wong, 2018, Quantitative activity profile and context dependence of all human 5′ splice sites, Mol. Cell, 71, 1012, 10.1016/j.molcel.2018.07.033 Hiller, 2007, Pre-mRNA secondary structures influence exon recognition, PLoS Genet., 3, 10.1371/journal.pgen.0030204 Singh, 2007, Modulating role of a RNA structure in skipping of a critical exon in the spinal muscular atrophy genes, Nucleic Acids Res., 35, 371, 10.1093/nar/gkl1050 Buratti, 2007, RNA structure is a key regulatory element in pathological ATM and CFTR pseudoexon inclusion events, Nucleic Acids Res., 35, 4369, 10.1093/nar/gkm447 Warf, 2010, Role of RNA structure in regulating pre-mRNA splicing, Trends Biochem. Sci., 35, 169, 10.1016/j.tibs.2009.10.004 Pervouchine, 2012, Evidence for widespread association of mammalian splicing and conserved long-range RNA structures, RNA, 18, 1, 10.1261/rna.029249.111 Singh, 2013, An intronic structure enabled by a long-distance interaction serves as a novel target for splicing correction in spinal muscular atrophy, Nucleic Acids Res., 41, 8144, 10.1093/nar/gkt609 Singh, 2015, Splicing regulation in spinal muscular atrophy by a RNA structure formed by long distance interactions, Ann. N.Y. Acad. Sci., 1341, 176, 10.1111/nyas.12727 Wilusz, 2018, A 360° view of circular RNAs: from biogenesis to functions, Wiley Interdiscip. Rev. RNA, 9, 10.1002/wrna.1478 Wan, 2011, Understanding the transcriptome through RNA structure, Nat. Rev. Genet., 12, 641, 10.1038/nrg3049 Peschek, 2015, A conformational RNA zipper promotes intron ejection during non-conventional XBP1 mRNA splicing, EMBO Rep., 16, 1688, 10.15252/embr.201540955 Preußner, 2017, Body temperature cycles control rhythmic alternative splicing in mammals, Mol. Cell., 67, 433, 10.1016/j.molcel.2017.06.006 Saldi, 2016, Coupling of RNA polymerase II transcription elongation with pre-mRNA splicing, J. Mol. Biol., 428, 2623, 10.1016/j.jmb.2016.04.017 Dujardin, 2013, Transcriptional elongation and alternative splicing, Biochim. Biophys. Acta, 1829, 134, 10.1016/j.bbagrm.2012.08.005 Nieto Moreno, 2015, Chromatin, DNA structure and alternative splicing, FEBS Lett., 589, 3370, 10.1016/j.febslet.2015.08.002 Zhang, 2016, A two-way street: regulatory interplay between RNA polymerase and nascent RNA structure, Trends Biochem. Sci., 41, 293, 10.1016/j.tibs.2015.12.009 Lefebvre, 1995, Identification and characterization of a spinal muscular atrophy-determining gene, Cell, 80, 155, 10.1016/0092-8674(95)90460-3 Singh, 2017, Diverse role of survival motor neuron protein, Biochim. Biophys. Acta Gene Regul. Mech., 1860, 299, 10.1016/j.bbagrm.2016.12.008 Ottesen, 2018, High-affinity RNA targets of the Survival Motor Neuron protein reveal diverse preferences for sequence and structural motifs, Nucleic Acids Res., 46, 10983 Price, 2018, RNP assembly defects in spinal muscular atrophy, Adv. Neurobiol., 20, 143, 10.1007/978-3-319-89689-2_6 Lorson, 1999, A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy, Proc. Natl. Acad. Sci. U. S. A., 11, 6307, 10.1073/pnas.96.11.6307 Monani, 1999, A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2, Hum. Mol. Genet., 8, 1177, 10.1093/hmg/8.7.1177 Singh, 2007, Evolving concepts on human SMN pre-mRNA splicing, RNA Biol., 4, 7, 10.4161/rna.4.1.4535 Singh, 2011, Alternative splicing in spinal muscular atrophy underscores the role of an intron definition model, RNA Biol., 8, 600, 10.4161/rna.8.4.16224 Singh, 2017, Transcription and splicing regulation of spinal muscular atrophy genes, 75 Singh, 2018, Mechanism of splicing regulation of spinal muscular atrophy genes, Adv. Neurobiol., 20, 31, 10.1007/978-3-319-89689-2_2 Ahmad, 2016, Molecular mechanisms of neurodegeneration in spinal muscular atrophy, J. Exp. Neurosci., 10, 39, 10.4137/JEN.S33122 Nash, 2016, Spinal muscular atrophy: more than a disease of motor neurons?, Curr. Mol. Med., 16, 779, 10.2174/1566524016666161128113338 Lipnick, 2019, Systemic nature of spinal muscular atrophy revealed by studying insurance claims, PLoS One, 14, 10.1371/journal.pone.0213680 Ottesen, 2016, Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy, Sci. Rep., 6, 20193, 10.1038/srep20193 Howell, 2017, TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy, Sci. Rep., 7, 7183, 10.1038/s41598-017-07468-2 Howell, 2017, Gender-specific amelioration of SMA phenotype upon disruption of a deep intronic structure by an oligonucleotide, Mol. Ther., 25, 1328, 10.1016/j.ymthe.2017.03.036 Ottesen, 2017, ISS-N1 makes the first FDA-approved drug for spinal muscular atrophy, Transl. Neurosci., 8, 1, 10.1515/tnsci-2017-0001 Singh, 2017, How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy, Gene Ther., 24, 520, 10.1038/gt.2017.34 Singh, 2006, Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron, Mol. Cell. Biol., 26, 1333, 10.1128/MCB.26.4.1333-1346.2006 Singh, 2015, Mechanistic principles of antisense targets for the treatment of spinal muscular atrophy, Future Med. Chem., 7, 1793, 10.4155/fmc.15.101 Singh, 2009, A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy, RNA Biol., 6, 341, 10.4161/rna.6.3.8723 Hua, 2008, Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice, Am. J. Hum. Genet., 82, 834, 10.1016/j.ajhg.2008.01.014 Singh, 2017, Activation of a cryptic 5′ splice site reverses the impact of pathogenic splice site mutations in the spinal muscular atrophy gene, Nucleic Acids Res., 45, 12214, 10.1093/nar/gkx824 Singh, 2011, TIA1 prevents skipping of a critical exon associated with spinal muscular atrophy, Mol. Cell. Biol., 1, 935, 10.1128/MCB.00945-10 Dal Mas, 2015, Improvement of SMN2 pre-mRNA processing mediated by exon-specific-U1-small nuclear RNA, Am. J. Hum. Genet., 96, 93, 10.1016/j.ajhg.2014.12.009 Rogalska, 2016, Therapeutic activity of modified U1 core spliceosomal particles, Nat. Commun., 7, 11168, 10.1038/ncomms11168 Singh, 2019, A novel role of U1 snRNP: splice site selection from a distance, Biochim. Biophys. Acta, 1862, 634, 10.1016/j.bbagrm.2019.04.004 Palacino, 2015, SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice, Nat. Chem. Biol., 11, 511, 10.1038/nchembio.1837 Sivaramakrishnan, 2017, Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers, Nat. Commun., 8, 1476, 10.1038/s41467-017-01559-4 Wang, 2018, Mechanistic studies of a small-molecule modulator of SMN2 splicing, Proc. Natl. Acad. Sci. U. S. A., 115, E4604, 10.1073/pnas.1800260115 Garcia-Lopez, 2018, Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes, Nat. Commun., 9, 2032, 10.1038/s41467-018-04110-1 Singh, 2004, The regulation and regulatory activities of alternative splicing of the SMN gene, Crit. Rev. Eukaryot. Gene Expr., 14, 271, 10.1615/CritRevEukaryotGeneExpr.v14.i4.30 Singh, 2004, An extended inhibitory context causes skipping of exon 7 of SMN2 in spinal muscular atrophy, Biochem. Biophys. Res. Commun., 315, 381, 10.1016/j.bbrc.2004.01.067 Kashima, 2003, A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy, Nat. Genet., 34, 460, 10.1038/ng1207 Cartegni, 2002, Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1, Nat. Genet., 30, 377, 10.1038/ng854 Hua, 2007, Enhancement of SMN2 exon 7 inclusion by antisense oligonucleotides targeting the exon, PLoS Biol., 5, 10.1371/journal.pbio.0050073 Singh, 2007, Unfolding the mystery of alternative splicing through a unique method of in vivo selection, Front. Biosci., 12, 3263, 10.2741/2310 Singh, 2004, In vivo selection reveals features of combinatorial control that defines a critical exon in the spinal muscular atrophy genes, RNA, 10, 1291, 10.1261/rna.7580704 Xiong, 2015, RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease, Science, 347, 10.1126/science.1254806 Keil, 2014, A short antisense oligonucleotide ameliorates symptoms of severe mouse models of spinal muscular atrophy, Mol. Ther. Nucleic Acids, 3, 10.1038/mtna.2014.23 Taube, 2014, PMD patient mutations reveal a long-distance intronic interaction that regulates PLP1/DM20 alternative splicing, Hum. Mol. Genet., 23, 5464, 10.1093/hmg/ddu271 Deininger, 2011, Alu elements: know the SINEs, Genome Biol., 12, 236, 10.1186/gb-2011-12-12-236 Daniel, 2014, Alu elements shape the primate transcriptome by cis-regulation of RNA editing, Genome Biol., 15, R28, 10.1186/gb-2014-15-2-r28 Ottesen, 2017, A multilayered control of the human Survival Motor Neuron gene expression by Alu elements, Front. Microbiol., 8, 2252, 10.3389/fmicb.2017.02252 Wilusz, 2015, Repetitive elements regulate circular RNA biogenesis, Mob. Genet. Elem., 5, 1, 10.1080/2159256X.2015.1045682 Zhang, 2014, Complementary sequence-mediated exon circularization, Cell, 159, 134, 10.1016/j.cell.2014.09.001