Investigators exploring the use of Morpholino oligos to modify poly-A tailing of mRNAs.
Vorlova S, Blahetek G, Barbieri R, Kerstan Y, Rosa A, Bundalo M, Egg M, Butt E, Henke E, Dölken L, Houben R, Schilling B, Fischer U, Erhard F, Zernecke A. U1 snRNP suppresses microRNA biogenesis by alternative intronic polyadenylation in melanoma. bioRxiv. 2022;[preprint] doi:10.1101/2022.06.01.479622 Marchalot A, Horiot C, Lambert J-M, Carrion C, Oblet C, Pollet J, Cogné M, Moreau J, Laffleur B, Delpy L. Targeting IgE polyadenylation signal with antisense oligonucleotides decreases IgE secretion and plasma cell viability. J Allergy Clin Immunol. 2021;[Epub ahead of print] doi:10.1016/j.jaci.2021.09.039 Lu-Nguyen N, Malerba A, Dickson G, Popplewell L. Systemic antisense therapeutics inhibiting DUX4 expression improves muscle function in an FSHD mouse model. bioRxiv. 2021;[preprint] doi:10.1101/2021.01.14.426659
Targeting polyadenylation signal and cleavage site on DUX4 3'-UTR; Multiple doses of Vivo-Morpholinos in mice at 10 mg/kg, i.p. injection Di C, So BR, Cai Z, Arai C, Duan J, Dreyfuss G. U1 snRNP Telescripting Roles in Transcription and Its Mechanism. Cold Spring Harb Symp Quant Biol. 2020 Jun 9:040451. doi:10.1101/sqb.2019.84.040451. Online ahead of print. Naveed A, Cooper JA, Li R, Hubbard A, Liu T, Wilton S, Fletcher S, Fox A. PolyA-modulating antisense oligonucleotides reveal opposing functions for long non-coding RNA NEAT1 isoforms in neuroblastoma. bioRxiv. 2020;[preprint] doi:10.1101/2020.05.01.071696 Golshirazi G, Ciszewski L, Lu-Nguyen N, Popplewell L. Antisense Oligonucleotide Targeting of 3'-UTR of mRNA for Expression Knockdown. Methods Mol Biol. 2018;1828:91-124. doi: 10.1007/978-1-4939-8651-4_6. Van Etten JL, Nyquist M, Li Y, Yang R, Ho Y, Johnson RM, Ondigi O, Voytas DF, Henzler C, Dehm SM. Targeting a single alternative polyadenylation site coordinately blocks expression of androgen receptor mRNA splice variants in prostate cancer. Cancer Res. 2017 Aug 15. pii: canres.0320.2017. doi: 10.1158/0008-5472.CAN-17-0320. [Epub ahead of print] Gong Q, Zhou Z. Regulation of Isoform Expression by Blocking Polyadenylation Signal Sequences with Morpholinos. Methods Mol Biol. 2017;1565:141-150. doi: 10.1007/978-1-4939-6817-6_12. Mueller AA, van Velthoven CT, Fukumoto KD, Cheung TH, Rando TA. Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis. Nature. 2016 Nov 28. doi: 10.1038/nature20160. [Epub ahead of print]
Vivo-MO in mouse targeting intronic poly-A site, another for a splice site.] Chen JC, King OD, Zhang Y, Clayton NP, Spencer C, Wentworth BM, Emerson CP Jr, Wagner KR. Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics. Mol Ther. 2016 Jul 5. doi: 10.1038/mt.2016.111. [Epub ahead of print] Marsollier AC, Ciszewski L, Mariot V, Popplewell L, Voit T, Dickson G, Dumonceaux J. Antisense targeting of 3'end elements involved in DUX4 mRNA processing is an efficient therapeutic strategy for Facioscapulohumeral Dystrophy: a new gene silencing approach. Hum Mol Genet. 2016 Jan 19. pii: ddw015. [Epub ahead of print] Makino S, Mishima Y, Inoue K, Inada T. Roles of mRNA fate modulators Dhh1 and Pat1 in TNRC6-dependent gene silencing recapitulated in yeast. J Biol Chem. 2015 Mar 27;290(13):8331-47. doi: 10.1074/jbc.M114.615088. Epub 2015 Feb 5. Gong Q, Stump MR, Zhou Z. Upregulation of Functional Kv11.1 Isoform Expression by Inhibition of Intronic Polyadenylation with Antisense Morpholino Oligonucleotides. J Mol Cell Cardiol. 2014 Nov;76:26-32. doi: 10.1016/j.yjmcc.2014.08.007. Epub 2014 Aug 14. Uehara H, Cho Y, Simonis J, Cahoon J, Archer B, Luo L, Das SK, Singh N, Ambati J, Ambati BK. Dual suppression of hemangiogenesis and lymphangiogenesis by splice-shifting morpholinos targeting vascular endothelial growth factor receptor 2 (KDR). FASEB J, 2012;[Epub ahead of print] doi:10.1096/fj.12-213835 Wada T, Hara M, Taneda T, Qingfu C, Takata R, Moro K, Takeda K, Kishimoto T, Handa H. Antisense morpholino targeting just upstream from a poly(A) tail junction of maternal mRNA removes the tail and inhibits translation. Nucl Acids Res. 2012;[Epub ahead of print] doi:10.1093/nar/gks765 Vorlová S, Rocco G, LeFave CV, Jodelka FM, Hess K, Hastings ML, Henke H, Cartegni L. Induction of Antagonistic Soluble Decoy Receptor Tyrosine Kinases by Intronic PolyA Activation. Mol Cell. 2011;(43)6:927-39.