Natural antisense transcripts: Biology, mechanisms, and therapeutic potential: An update
DOI:
https://doi.org/10.25081/imrj.2026.v16.10071Keywords:
Natural antisense transcripts, Long non-coding RNA, Gene regulation, Antisense oligonucleotides, RNA therapeutics, Epigenetics and transcriptional regulationAbstract
Endogenous RNA molecules called natural antisense transcripts (NATs) are produced from the complementary DNA strand of either non-coding or protein-coding genes. NATs are not byproducts of random transcription but rather important controllers of gene expression, according to mounting evidence. Antisense transcription has been demonstrated to occur extensively in both prokaryotic and eukaryotic genomes with the development of high-throughput sequencing technology, highlighting its biological significance and evolutionary conservation. Numerous processes, such as transcriptional inhibition, chromatin remodeling, epigenetic changes, RNA editing, alternative splicing, regulation of mRNA stability, and translational control, are used by NATs to control gene expression. As a result, they play essential roles in numerous physiological processes, such as embryonic development, cell differentiation, adaptation to stress, and the maintenance of normal cellular homeostasis. Dysregulation of NAT expression has been linked to a variety of illnesses, including cancer, neurological disorders, cardiovascular diseases, metabolic disorders, and autoimmune problems. NATs play important roles in plant development and stress biology. This review highlights current knowledge on NAT biogenesis, classification, and structural organization in the initial chapter by providing a brief introduction to transcription mechanisms and players involved. The following sections cover the molecular mechanisms, biological roles of NATs. The role of NATs in human diseases and plant biology forms the later chapter. The emerging therapeutic applications of NATs are discussed in the last chapter. With the availability of the genomes of several genomes and parallel developments in bioinformatics, antisense biology stands at an exciting junction to address several basic questions and applications.
Downloads
References
Alberts, B., Heald, R., Johnson, A., Morgan, D., Raff, M., Roberts, K., Walter, P., Wilson, J., & Hunt, T. (2022). Molecular biology of the cell. (7th ed.). W. W. Norton & Company.
Ali, A., Khatoon, A., Shao, C., Murtaza, B., Tanveer, Q., & Su, Z. (2024). Therapeutic potential of natural antisense transcripts and various mechanisms involved for clinical applications and disease prevention. RNA Biology, 21(1), 127-144. https://doi.org/10.1080/15476286.2023.2293335
Amanat, M., Nemeth, C. L., Fine, A. S., Leung, D. G., & Fatemi, A. (2022). Antisense oligonucleotide therapy for the nervous system: From bench to bedside with emphasis on pediatric neurology. Pharmaceutics, 14(11), 2389. https://doi.org/10.3390/pharmaceutics14112389
Arning, L., & Nguyen, H. P. (2022). Huntington disease update: New insights into the role of repeat instability in disease pathogenesis. Medical Genetics, 33(4), 293-300. https://doi.org/10.1515/medgen-2021-2101
Azman, K. F., & Zakaria, R. (2022). Recent advances on the role of brain-derived neurotrophic factor (BDNF) in neurodegenerative diseases. International Journal of Molecular Sciences, 23(12), 6827. https://doi.org/10.3390/ijms23126827
Bach, S. V., Punzi, G., Smith, N. E., Mukherjee, S., Shin, J. H., Chen, Q., Pertea, G., Collado-Torres, L., Maynard, K. R., Page, S. C., Kleinman, J. E., Hyde, T. M., Weinberger, D. R., Martinowich, K., & Ursini, G. (2025). BDNF-DT and BDNF-AS-DT: Novel genes in the BDNF locus [Preprint]. medRxiv. https://doi.org/10.1101/2025.07.10.25331311
Bazzari, A. H., & Bazzari, F. H. (2022). BDNF therapeutic mechanisms in neuropsychiatric disorders. International Journal of Molecular Sciences, 23(15), 8417. https://doi.org/10.3390/ijms23158417
Bhale, A. S., & Venkataraman, K. (2022). Leveraging knowledge of HDL's major protein ApoA1: Structure, function, mutations, and potential therapeutics. Biomedicine & Pharmacotherapy, 154, 113634. https://doi.org/10.1016/j.biopha.2022.113634
Bhaumik, S. R. (2011). Distinct regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID. Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanisms, 1809(2), 97-108. https://doi.org/10.1016/j.bbagrm.2010.08.009
Borsani, O., Zhu, J., Verslues, P. E., Sunkar, R., & Zhu, J.-K. (2005). Endogenous siRNAs derived from a pair of natural cis-antisense transcripts regulate salt tolerance in Arabidopsis. Cell, 123(7), 1279-1291. https://doi.org/10.1016/j.cell.2005.11.035
Cao, J., & Kapranov, P. (2022). Methods to analyze the non-coding RNA interactome—Recent advances and challenges. Frontiers in Genetics, 13, 857759. https://doi.org/10.3389/fgene.2022.857759
Chavali, P. L., Ramachandran, R., & Chavali, S. (2020). Functional categories of RNA regulation. In R. Pandey (Ed.), RNA-based regulation in human health and disease (Vol. 19, pp. 59-83). Academic Press. https://doi.org/10.1016/B978-0-12-817193-6.00003-0
Colucci-D'Amato, L., Speranza, L., & Volpicelli, F. (2020). Neurotrophic factor BDNF: Physiological functions and therapeutic potential in depression, neurodegeneration, and brain cancer. International Journal of Molecular Sciences, 21(20), 7777. https://doi.org/10.3390/ijms21207777
Crooke, S. T., Baker, B. F., Crooke, R. M., & Liang, X.-H. (2021). Antisense technology: An overview and prospectus. Nature Reviews Drug Discovery, 20, 427-453. https://doi.org/10.1038/s41573-021-00162-z
Csorba, T., Questa, J. I., Sun, Q., & Dean, C. (2014). Antisense COOLAIR mediates the coordinated switching of chromatin states at FLC during vernalization. Proceedings of the National Academy of Sciences, 111(45), 16160-16165. https://doi.org/10.1073/pnas.1419030111
Dubey, A. K., Kumar, A., Nurbekova, Z., & Kumar, N. (2026). Long non-coding RNAs in human disease: An overview of biogenesis, molecular mechanisms, and therapeutic opportunities. Current Issues in Molecular Biology, 48(4), 414. https://doi.org/10.3390/cimb48040414
Fachel, A. A., Tahira, A. C., Vilella-Arias, S. A., Maracaja-Coutinho, V., Gimba, E. R. p., Vignal, G. M., Campos, F. S., Reis, E. M., & Verjovski-Almeida, S. (2013). Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: Emerging functional associations. Molecular Cancer, 12, 140. https://doi.org/10.1186/1476-4598-12-140
Faghihi, M. A., Modarresi, F., Khalil, A. M., Wood, D. E., Sahagan, B. G., Morgan, T. E., Finch, C. E., St. Laurent, G., Kenny, P. J., & Wahlestedt, C. (2008). Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of β-secretase. Nature Medicine, 14, 723-730. https://doi.org/10.1038/nm1784
Fan, S., Yang, H., Hu, Y., Zhang, L., & Huang, M. (2026). A review of the advances and perspectives in sequencing technologies for analysing plant epigenetic responses to abiotic stress. Plant Stress, 19, 101144. https://doi.org/10.1016/j.stress.2025.101144
Gendron, T. F., Bieniek, K. F., Zhang, Y.-J., Jansen-West, K., Ash, P. E. A., Caulfield, T., Duaghrity, L., Dunmore, J. H., Castanedes-Casey, M., Chew, J., Cosio, D. M., van Blitterswijk, M., Lee, W. C., Rademakers, R., Boylan, K. B., Dickson, D. W., & Petrucelli, L. (2013). Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS. Acta Neuropathologica, 126, 829-844. https://doi.org/10.1007/s00401-013-1192-8
Golomb, R., Yoles, M., Fishilevich, S. Cohen, B., Peled, S. S., Dahary, D., Gokhman, D., & Pilpel, Y. (2026). An information content principle explains regulatory patterns of gene expression across human tissues. Nature Communications, 17, 5064. https://doi.org/10.1038/s41467-026-71279-1
Grigore, A., & Goebel, L. J. (2025). Frontotemporal dementia and amyotrophic lateral sclerosis: A case report and clinical insights. Cureus, 17(3), e80329. https://doi.org/10.7759/cureus.80329
Guéant, J. L., Siblini, Y., Chéry, C., Schmitt, G., Guéant-Rodriguez, R. M., Coelho, D., Watkins, D., Rosenblatt, D. S., & Oussalah, A. (2022). Epimutation in inherited metabolic disorders: the influence of aberrant transcription in adjacent genes. Human Genetics, 141(7), 1309-1325. https://doi.org/10.1007/s00439-021-02414-9
Guo, Y., Shang, X., Ma, L., Cao, Y. (2024). RNA-binding protein-mediated alternative splicing regulates abiotic stress responses in plants. International Journal of Molecular Sciences, 25(19), 10548. https://doi.org/10.3390/ijms251910548
Halley, P., Kadakkuzha, B. M., Faghihi, M. A., Magistri, M., Zeier, Z., Khorkova, O., Coito, C., Hsiao, J., Lawrence, M., & Wahlestedt, C. (2014). Regulation of the apolipoprotein gene cluster by a long noncoding RNA. Cell Reports, 6(1), 222-230. https://doi.org/10.1016/j.celrep.2013.12.015
Hamada, M., Varkoly, K. S., Riyadh, O., Beladi, R., Munuswamy-Ramanujam, G., Rawls, A., Wilson-Rawls, J., Chen, H., McFadden, G., & Lucas, A. R. (2024). Urokinase-type plasminogen activator receptor (uPAR) in inflammation and disease: A unique inflammatory pathway activator. Biomedicines, 12(6), 1167. https://doi.org/10.3390/biomedicines12061167
Hampel, H., Vassar, R., De Strooper, B., Hardy, J., Willem, M., Singh, N., Zhou, J., Yan, R., Vanmechelen, E., De Vos, A., Nisticò, R., Corbo, M., Imbimbo, B. P., Streffer, J., Voytyuk, I., Timmers, M., Tahami Monfared, A. A., Irizarry, M., Albala, B., ... Vergallo, A. (2021). The β-secretase BACE1 in Alzheimer's disease. Biological Psychiatry, 89(8), 745-756. https://doi.org/10.1016/j.biopsych.2020.02.001
Heo, J. B., & Sung, S. (2011). Vernalization-mediated epigenetic silencing by a long intronic noncoding RNA. Science, 331(6013), 76-79. https://doi.org/10.1126/science.1197349
Huang, H., Li, L., & Wen, K. (2021). Interactions between long non-coding RNAs and RNA-binding proteins in cancer (Review). Oncology Reports, 46(6), 256. https://doi.org/10.3892/or.2021.8207
Huang, M., Chen, W., Qi, F., Xia, R., Sun, M., Xu, T. P., Yin, L., Zhang, E. B., De, W., & Shu, Y. Q. (2015). Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2. Journal of Hematology & Oncology, 8, 57. https://doi.org/10.1186/s13045-015-0153-1
Isom, L. L., & Knupp, K. G. (2021). Dravet Syndrome: Novel approaches for the most common genetic epilepsy. Neurotherapeutics, 18(3), 1524-1534.
Iyengar, B. R., Grandchamp, A., & Bornberg-Bauer, E. (2024). How antisense transcripts can evolve to encode novel proteins. Nature Communications, 15, 6187. https://doi.org/10.1038/s41467-024-50550-3
Jalaiei, A., Kiani Darabi, A. H., Sakkaki, E., Rezazadeh, M., & Ghafouri-Fard, S. (2026). Molecular interplay between non-coding RNAs and BDNF in neurodegenerative disorders: A systematic review. Molecular Biology Reports, 53, 901. https://doi.org/10.1007/s11033-026-12067-4
Jiménez-Trejo, F., Jiménez-García, K. L., & Canul-Medina, G. (2024). Serotonin and schizophrenia: What influences what? Frontiers in Psychiatry, 15, 1451248. https://doi.org/10.3389/fpsyt.2024.1451248
Kang, H. R., Zaric, V., Rybalchenko, V., Gray, S. J., & Butler, R. K. (2026). RNAi-Induced Expression of Paternal UBE3A. Genes, 17(2), 156. https://doi.org/10.3390/genes17020156
Katayama, S., Tomaru, Y., Kasukawa, T., Waki, K., Nakanishi, M., Nakamura, M., Nishida, H., Yap, C. C., Suzuki, M., Kawai, J., Suzuki, H., Carninci, P., Hayashizaki, Y., Wells, C., Frith, M., Ravasi, T., Pang, K. C., Hallinan, J., Mattick, J., ... FANTOM Consortium. (2005). Antisense transcription in the mammalian transcriptome. Science, 309(5740), 1564-1566. https://doi.org/10.1126/science.1112009
Keegan, L. P., Hajji, K., & O'Connell, M. A. (2023). Adenosine Deaminase Acting on RNA (ADAR) enzymes: A journey from weird to wondrous. Accounts of Chemical Research, 56(22), 3165-3174. https://doi.org/10.1021/acs.accounts.3c00433
Khorkova, O., Stahl, J., Joji, A., Volmar, C. H., Zeier, Z., & Wahlestedt, C. (2022). Natural antisense transcripts as drug targets. Frontiers in Molecular Biosciences, 9, 978375. https://doi.org/10.3389/fmolb.2022.978375
Korf, H.-W., & von Gall, C. (2022). Circadian physiology. In D. W. Pfaff, N. D. Volkow, J. L. Rubenstein (Eds.), Neuroscience in the 21st Century (pp. 2541-2576). Springer. https://doi.org/10.1007/978-3-030-88832-9_65
Krappinger, J. C., Bonstingl, L., Pansy, K., Sallinger, K., Wreglesworth, N. I., Grinninger, L., Deutsch, A., El-Heliebi, A., Kroneis, T., McFarlane, R. J., Sensen, C. W., & Feichtinger, J. (2021). Non-coding natural antisense transcripts: Analysis and application. Journal of Biotechnology, 340, 75-101. https://doi.org/10.1016/j.jbiotec.2021.08.005
Krzyczmonik, K., Wroblewska-Swiniarska, A., & Swiezewski, S. (2017). Developmental transitions in Arabidopsis are regulated by antisense RNAs resulting from bidirectionally transcribed genes. RNA Biology, 14(7), 838-842. https://doi.org/10.1080/15476286.2017.1327112
Layer, J. H., & Weil, P. A. (2009). Ubiquitous antisense transcription in eukaryotes: Novel regulatory mechanism or byproduct of opportunistic RNA polymerase? F1000 Biology Reports, 1, 33. https://doi.org/10.3410/B1-33
Lee, D., Chen, W., Kaku, H. N., Zhuo, X., Chao, E. S., Soriano, A., Kuncheria, A., Flores, S., Kim, J. H., Rivera, A., Rigo, F., Jafar-Nejad, P., Beaudet, A. L., Caudill, M. S., & Xue, M. (2023). Antisense oligonucleotide therapy rescues disturbed brain rhythms and sleep in juvenile and adult mouse models of Angelman syndrome. eLife, 12, e81892. https://doi.org/10.7554/eLife.81892
Lehner, B., Williams, G., Campbell, R. D., & Sanderson, C. M. (2002). Antisense transcripts in the human genome. Trends in Genetics, 18(2), 63-65. https://doi.org/10.1016/S0168-9525(02)02598-2
Lersch, R., Jannadi, R., Grosse, L., Wagner, M., Schneider, M. F., von Stülpnagel, C., Heinen, F., Potschka, H., & Borggraefe, I. (2023). Targeted molecular strategies for genetic neurodevelopmental disorders: Emerging lessons from Dravet syndrome. The Neuroscientist, 29(6), 732-750. https://doi.org/10.1177/10738584221088244
Li, F., Wang, Y., Yang, H., Xu, Y., Zhou, X., Zhang, X., Xie, Z., & Bi, J. (2019). The effect of BACE1-AS on β-amyloid generation by regulating BACE1 mRNA expression. BMC Molecular Biology, 20(1), 23. https://doi.org/10.1186/s12867-019-0140-0
Ling, M. H. T., Ban, Y., Wen, H., Wang, S. M., & Ge, S. X. (2013). Conserved expression of natural antisense transcripts in mammals. BMC Genomics, 14, 243. https://doi.org/10.1186/1471-2164-14-243
Liu, L., Chen, X., Zhang, Y., Hu, Y., Shen, X., & Zhu, W. (2017). Long non-coding RNA TUG1 promotes endometrial cancer development via inhibiting miR-299 and miR-34a-5p. Oncotarget, 8, 31386-31394. https://doi.org/10.18632/oncotarget.15607
Liu, X., Fu, M., Xia, D., Ji, Z., Hu, N., Leng, Z., Xie, W., Fang, Y., & Zhang, J. (2022). Overexpression of FAM83A is associated with poor prognosis of lung adenocarcinoma. Journal of Oncology, 2022, 8767333. https://doi.org/10.1155/2022/8767333
Lou, Z., Zhu, J., Li, X., Li, X., Du, K., Wang, B., Zhang, F., & Zhang, X. (2021). LncRNA Sirt1-AS upregulates Sirt1 to attenuate aging-related deep venous thrombosis. Aging, 13(5), 6918-6935. https://doi.org/10.18632/aging.202550
Maranga, C., Fernandes, T. G., Bekman, E., & da Rocha, S. T. (2020). Angelman syndrome: A journey through the brain. The FEBS Journal, 287(11), 2154-2175. https://doi.org/10.1111/febs.15258
Massone, S., Vassallo, I., Fiorino, G., Castelnuovo, M., Barbieri, F., Borghi, R., Tabaton, M., Robello, M., Gatta, E., Russo, C., Florio, T., Dieci, G., Cancedda, R., & Pagano, A. (2011). 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiology of Disease, 41(2), 308-317. https://doi.org/10.1016/j.nbd.2010.09.019
Meng, L., Person, R. E., Huang, W., Zhu, P. J., Costa-Mattioli, M., & Beaudet, A. L. (2013). Truncation of Ube3a-ATS unsilences paternal Ube3a and ameliorates behavioral defects in the Angelman syndrome mouse model. PLoS Genetics, 9(12), e1004039. https://doi.org/10.1371/journal.pgen.1004039
Meseure, D., Vacher, S., Drak Alsibai, K., Nicolas, A., Chemlali, W., Caly, M., Lidereau, R., Pasmant, E., Callens, C., & Bièche, I. (2016). Expression of ANRIL–Polycomb complexes–CDKN2A/B/ARF genes in breast tumors: Identification of a two-gene (EZH2/CBX7) signature with independent prognostic value. Molecular Cancer Research, 14(7), 623-633. https://doi.org/10.1158/1541-7786.MCR-15-0418
Miller, R. H., Zimmer, A., Moutot, G., Mesnard, J.-M., & Chazal, N. (2021). Retroviral Antisense Transcripts and Genes: 33 Years after First Predicted, a Silent Retroviral Revolution? Viruses, 13(11), 2221. https://doi.org/10.3390/v13112221
Mills, J. D., Chen, B. J., Ueberham, U., Arendt, T., & Janitz, M. (2016). The antisense transcriptome and the human brain. Journal of Molecular Neuroscience, 58, 1-15. https://doi.org/10.1007/s12031-015-0694-3
Misra, S., Crosby, M. A., Mungall, C. J., Matthews, B. B., Campbell, K. S., Hradecky, P., Huang, Y., Kaminker, J. S., Millburn, G. H., Prochnik, S. E., Smith, C. D., Tupy, J. L., Whitfield, E. J., Bayraktaroglu, L., Berman, B. P., Bettencourt, B. R., Celniker, S. E., de Grey, A. D. N. J., Drysdale, R. A., ... Lewis, S. E. (2002). Annotation of the Drosophila melanogaster euchromatic genome: A systematic review. Genome Biology, 3(12), research0083. https://doi.org/10.1186/gb-2002-3-12-research0083
Modarresi, F., Faghihi, M. A., Lopez-Toledano, M. A., Fatemi, R. P., Magistri, M., Brothers, S. P., van der Brug, M., & Wahlestedt, C. (2012). Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nature Biotechnology, 30, 453-459. https://doi.org/10.1038/nbt.2158
Molias, F. B., Sim, A., Leong, K. W., An, O., Song, Y., Ng, V. H. E., Lim, M. W. J., Ying, C., Teo, J. X. J., Göke, J., & Chen, L. (2021). Antisense RNAs influence promoter usage of their counterpart sense genes in cancer. Cancer Research, 81(23), 5849-5861. https://doi.org/10.1158/0008-5472.CAN-21-1859
Mosig, R. A., Castaneda, A. N., Deslauriers, J. C., Frazier, L. P., He, K. L., Maghzian, N., Pokharel, A., Schrier, C. T., Zhu, L., Koike, N., Tyson, J. J., Green, C. B., Takahashi, J. S., & Kojima, S. (2021). Natural antisense transcript of Period2, Per2AS, regulates the amplitude of the mouse circadian clock. Genes & Development, 35(11-12), 899-913. https://doi.org/10.1101/gad.343541.120.
Myers, K. A. (2023). SCN1A as a therapeutic target for Dravet syndrome. Expert Opinion on Therapeutic Targets, 27(6), 459-467. https://doi.org/10.1080/14728222.2023.2230364
Nakatake, R., Okuyama, T., Kimura, T., & Nishizawa, M. (2026). RNA duplex formation and competing endogenous RNA, proposed as mechanisms in regulating expression of natural antisense transcripts- from hypotheses to potential therapeutic applications. Frontiers in Molecular Biosciences, 13, 1800738. https://doi.org/10.3389/fmolb.2026.1800738
Oono, Y., Yazawa, T., Kanamori, H., Sasaki, H., Mori, S., & Matsumoto, T. (2017). Genome-wide analysis of rice cis-natural antisense transcription under cadmium exposure using strand-specific RNA sequencing. BMC Genomics, 18, 761. https://doi.org/10.1186/s12864-017-4108-5
Ortega, J. A., Liang, Z., Xu, J. K., & Gottwein, E. (2024). Retargeting target-directed microRNA-decay sites to highly expressed viral or cellular miRNAs. Nucleic Acids Research, 52(22), 14171-14183. https://doi.org/10.1093/nar/gkae1103
Osato, N., Yamada, H., Satoh, K., Ooka, H., Yamamoto, M., Suzuki, K., Kawai, J., Carninci, P., Ohtomo, Y., Murakami, K., Matsubara, K., Kikuchi, S., & Hayashizaki, Y. (2003). Antisense transcripts with rice full-length cDNAs. Genome Biology, 5, R5. https://doi.org/10.1186/gb-2003-5-1-r5
Ou, C., & Li, G. (2017). Long non-coding RNA TUG1: a novel therapeutic target in small cell lung cancer. Journal of Thoracic Disease, 2017, 9(7), E644-E645. https://doi.org/10.21037/jtd.2017.06.94
Pelechano, V., & Steinmetz, L. M. (2013). Gene regulation by antisense transcription. Nature Reviews Genetics, 14, 880-893. https://doi.org/10.1038/nrg3594
Qiu, G.-Z., Tian, W., Fu, H.-T., Li, C.-P., & Liu, B. (2016). Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction. Biochemical and Biophysical Research Communications, 471(1), 135-141. https://doi.org/10.1016/j.bbrc.2016.01.164
Raswanthiya, S. P., Fernandes, O. P., Mathew, M. P., Balgote, P. J., & Sivaraman, J. (2026). Decoding BDNF in neurodevelopmental, neurodegenerative, and neurological disorders: Mechanisms and therapeutic perspectives. Molecular Biology Reports, 53, 330. https://doi.org/10.1007/s11033-026-11485-8
Rinaldi, C., & Wood, M. J. A. (2018). Antisense oligonucleotides: The next frontier for treatment of neurological disorders. Nature Reviews Neurology, 14, 9-21. https://doi.org/10.1038/nrneurol.2017.148
Rizzi, Y. S., Monteoliva, M. I., Fabro, G., Grosso, C. L., Laróvere, L. E., & Alvarez, M. E. (2015). P5CDH affects the pathways contributing to Pro synthesis after ProDH activation by biotic and abiotic stress conditions. Frontiers in Plant Science, 6, 00572. https://doi.org/10.3389/fpls.2015.00572
Ruiz, S. (2026). Exit from totipotency in mammals: an epigenetic perspective. Frontiers in Cell and Developmental Biology, 14, 1858789. https://doi.org/10.3389/fcell.2026.1858789
Ruttenberg, G. H. (2026). First computational characterization of HTR5A-AS1: A schizophrenia-linked antisense RNA with synaptic functions. Frontiers in Neuroscience, 20, 1716081. https://doi.org/10.3389/fnins.2026.1716081
Sanchez, A., Lhuillier, J., Grosjean, G., Ayadi, L., & Maenner, S. (2023). The long non-coding RNA ANRIL in cancers. Cancers, 15(16), 4160. https://doi.org/10.3390/cancers15164160
Santini, L., Yoshida, L., de Oliveira, K. D., Lembke, C. G., Diniz, A. L., Cantelli, G. C., Nishiyama-Junior, M. Y., & Souza, G. M. (2022). Antisense transcription in plants: A systematic review and an update on cis-NATs of sugarcane. International Journal of Molecular Sciences, 23(19), 11603. https://doi.org/10.3390/ijms231911603
Santos, F., Capela, A. M., Mateus, F., Nóbrega-Pereira, S., & Bernardes de Jesus, B. (2022). Non-coding antisense transcripts: Fine regulation of gene expression in cancer. Computational and Structural Biotechnology Journal, 20, 5652-5660. https://doi.org/10.1016/j.csbj.2022.10.009
Shahpari, M., Hashemi, M., Younesirad, T., Hasanzadeh, A., Mosanne, M., & Ahmadifard, M. (2024).The functional roles of competitive endogenous RNA (ceRNA) networks in apoptosis in human cancers: The circRNA/miRNA/mRNA regulatory axis and cell signaling pathways. Heliyon, 10(21), e37089. https://doi.org/10.1016/j.heliyon.2024.e37089
Shao, J., Chen, H., Yang, D., Jiang, M., Zhang, H., Wu, B., Li, J., Yuan, L., & Liu, C. (2017). Genome-wide identification and characterization of natural antisense transcripts by strand-specific RNA sequencing in Ganoderma lucidum. Scientific Reports, 7, 5711. https://doi.org/10.1038/s41598-017-04303-6
Shen, L., Ma, J., Li, P., Wu, Y., & Yu, H. (2023). Recent advances in the plant epitranscriptome. Genome Biology, 24, 43. https://doi.org/10.1186/s13059-023-02872-6
Su, W., Huo, Q., Wu, H., Wang, L., Ding, X., Liang, L., Zhou, L., Zhao, Y., Dan, J., & Zhang, H. (2021). The function of lncRNA H19 in cardiac hypertrophy. Cell & Bioscience, 11, 153. https://doi.org/10.1186/s13578-021-00668-4
Swiezewski, S., Liu, F., Magusin, A., & Dean, C. (2009). Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target. Nature, 462, 799-802. https://doi.org/10.1038/nature08618
Szczesniak, M. W., & Makalowska, I. (2016). lncRNA–RNA interactions across the human transcriptome. Plos One, 11(3), e0150353. https://doi.org/10.1371/journal.pone.0150353
Tang, R., Yin, L., Yao, L., Zhang, Q.-F., Chen, X.-P. (2023). A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα. Microbiology Spectrum, 11(3)3,2023,ISSN 2165-0497,https://doi.org/10.1128/spectrum.00733-23
Wahlestedt, C. (2013). Targeting long non-coding RNA to therapeutically upregulate gene expression. Nature Reviews Drug Discovery, 12, 433-446. https://doi.org/10.1038/nrd4018
Wang, H., Chung, P. J., Liu, J., Jang, I.-C., Kean, M. J., Xu, J., & Chua, N.-H. (2014). Genome-wide identification of long noncoding natural antisense transcripts and their responses to light in Arabidopsis. Genome Research, 24(3), 444-453. https://doi.org/10.1101/gr.165555.113
Wanowska, E., Kubiak, M. R., Rosikiewicz, W., Makałowska, I., & Szczęśniak, M. W. (2018). Natural antisense transcripts in diseases: From modes of action to targeted therapies. WIREs RNA, 9(2), e1461. https://doi.org/10.1002/wrna.1461
Werner, A., Kanhere, A., Wahlestedt, C., & Mattick, J. S. (2024). Natural antisense transcripts as versatile regulators of gene expression. Nature Reviews Genetics, 25, 730-744. https://doi.org/10.1038/s41576-024-00723-z
Wight, M., & Werner, A. (2013). The functions of natural antisense transcripts. Essays in Biochemistry, 54, 91-101. https://doi.org/10.1042/BSE0540091
Wright, B. W., Molloy, M. P., & Jaschke, P. R. (2022). Overlapping genes in natural and engineered genomes. Nature Reviews Genetics, 23, 154-168. https://doi.org/10.1038/s41576-021-00417-w
Wu, S., Chen, J., Liang, Y., Luo, Q., Tong, Y. Y., & Xie, L. (2022). Long non-coding RNA ZEB2-AS1 promotes hepatocellular carcinoma progression by regulating the miR-582-5p/FOXC1 axis. Cell Journal, 24(6), 285-293. https://doi.org/10.22074/cellj.2022.7963
Xu, J., Santos, R., & Li, H. (2017). Trans-acting regulation by natural antisense transcripts. RNA Biology, 14(9), 1234-1245. https://doi.org/10.1080/15476286.2017.1345678
Xu, J., Wang, Q., Freeling, M., Zhang, X., Xu, Y., Mao, Y., Tang, X., Wu, F., Lan, H., Cao, M., Rong, T., Lisch, D., & Lu, Y. (2017). Natural antisense transcripts are significantly involved in regulation of drought stress in maize, Nucleic Acids Research, 45(9), 5126-5141. https://doi.org/10.1093/nar/gkx085
Yang, F. (2022). Promoter antisense RNAs: Beyond transcription by-products of active promoters. RNA Biology, 19(1), 533-540. https://doi.org/10.1080/15476286.2022.2062177
Yassour, M., Pfiffner, J., Levin, J. Z., Adiconis, X., Gnirke, A., Nusbaum, C., Thompson, D.-A., Friedman, N., & Regev, A. (2010). Strand-specific RNA sequencing reveals extensive regulated long antisense transcripts that are conserved across yeast species. Genome Biology, 11, R87. https://doi.org/10.1186/gb-2010-11-8-r87
Yin, J., Luo, W., Zeng, X., Zeng, L., Li, Z., Deng, X., Tan, X., & Hu, W. (2017). UXT-AS1-induced alternative splicing of UXT is associated with tumor progression in colorectal cancer. American Journal of Cancer Research, 7(3), 462-472.
Yuan, Y., Lopez-Santiago, L., Denomme, N., Chen, C., O'Malley, H. A., Hodges, S. L., Ji, S., Han, Z., Christiansen, A., & Isom, L. L. (2024). Antisense oligonucleotides restore excitability, GABA signalling and sodium current density in a Dravet syndrome model. Brain, 147(4), 1231-1246. https://doi.org/10.1093/brain/awad349
Zhang, Q., & Liu, L. (2024). Novel insights into small open reading frame-encoded micropeptides in hepatocellular carcinoma: A potential breakthrough. Cancer Letters, 587, 216691. https://doi.org/10.1016/j.canlet.2024.216691
Zhang, X. (2024). Splice-switching antisense oligonucleotides for pediatric neurological disorders. Frontiers in Molecular Neuroscience, 17, 1412964. https://doi.org/10.3389/fnmol.2024.1412964
Zhang, Y., Lu, Y., Wang, N., Yang, Y., Hao, F., Fei, X., Chen, Y., & Wang, J. (2024). Alternative splicing-related long noncoding RNA ANRIL facilitates hepatocellular carcinoma by targeting the miR-199a-5p/SRSF1 axis and impacting Anillin. Molecular Carcinogenesis, 63(6), 1064-1078. https://doi.org/10.1002/mc.23709
Zhao, F., Yan, Y., Wang, Y., Liu, Y., & Yang, R. (2023a). Splicing complexity as a pivotal feature of alternative exons in mammalian species. BMC Genomics, 24, 198. https://doi.org/10.1186/s12864-023-09247-y
Zhao, Z., Chen, Y., Cheng, X., Huang, L., Wen, H., Xu, Q., Zhou, X., Zhang, X., Chen, J., & Ni, T. (2023b). The landscape of cryptic antisense transcription in human cancers reveals an oncogenic noncoding RNA in lung cancer. Science Advances, 9(14), eadf3264. https://doi.org/10.1126/sciadv.adf3264
Zhu, P., & Liu, H. (2026). LncRNA ZFAS1 in hepatocellular carcinoma: A systematic review of molecular mechanisms and clinical translation. Non-coding RNA Research, 17, 44-53. https://doi.org/10.1016/j.ncrna.2025.11.003
Published
How to Cite
Issue
Section
Copyright (c) 2026 M. D. Priya, B. K. Manjunath, P. K. Karibasappa, H. B. Kiran Kumar
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
.