Investigating Antisense Transcription at the HTT Locus


Antisense transcription is an important mechanism of gene expression regulation. Antisense RNAs play a role in mRNA processing, translation and epigenetic modifications of DNA and histones in the locus of their origin, leading to gene silencing. HTT is a widely expressed gene, the mutation of which causes Huntington’s disease. The product of the gene plays an important role in many cell processes, such as intracellular trafficking, cell division, autophagy, and others. An antisense transcription has been found at the HTT 5’-region. The HTT-AS gene has been reported to affect HTT expression in a Dicer-dependent manner. In this study, we analyzed extensive data from RNA-seq experiments for antisense transcription at the HTT locus. Antisense transcripts corresponding to the HTT-AS gene were not found. However, we revealed a number of antisense transcripts in different parts of the locus that may take part in the regulation and functioning of the HTT gene.

Keywords: antisense transcription, HTT-AS, HTTregulation, Huntington’s disease

[1] Li SH, Schilling G, Young WS et al. Huntington’s disease gene (IT15) is widely expressed in human and rat tissues. Neuron. 1993;11(5):985-993. doi:10.1016/0896- 6273(93)90127-d

[2] Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, LevorseJM,Tilghman SM. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature. 2000;405(6785):486-489. doi:10.1038/35013106

[3] Pelechano V, Steinmetz LM. Gene regulation by antisense transcription. Nature Reviews Genetics. 2013;14(12):880-893. doi:10.1038/nrg3594

[4] Chung DW, Rudnicki DD, Yu L, Margolis RL. A natural antisense transcript at the Huntington’s disease repeat locus regulates HTT expression. HumanMolecularGenetics. 2011;20(17):3467-3477. doi:10.1093/hmg/ddr263

[5] Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. JournalofMolecularBiology. 1990;215(3):403-410. doi:10.1016/S0022- 2836(05)80360-2

[6] Smit AFA, Hubley R, Green P. RepeatMasker annotation Open-4.0. 2013/01/01. Available for:

[7] Schwartz S, Zhang Z, Frazer KA et al. PipMaker–A web server for aligning two genomic DNA sequences. Genome Research. 2000;10(4):577-586. doi:10.1101/gr.10.4.577

[8] Kim D, Langmead B, Salzberg SL. HISAT: A fast spliced aligner with low memory requirements. Nature Methods. 2015;12(4):357-360. doi:10.1038/nmeth.3317

[9] Dobin A, Davis CA, Schlesinger F et al. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15-21. doi:10.1093/bioinformatics/bts635

[10] Kearse M, Moir R, Wilson A et al. Geneious. Bioinformatics.2012;28:1647–9.

[11] Pertea M, Pertea GM, Antonescu CM, Chang TC, Mendell JT, Salzberg SL. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nature Biotechnology. 2015;33(3):290-295. doi:10.1038/nbt.3122

[12] Grabherr MG, Haas BJ, Yassour M et al. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nature Biotechnology. 2011;29(7):644- 652. doi:10.1038/nbt.1883