Skip to main content

Advertisement

SpringerLink
Log in

The noncoding genome and hearing loss

  • Review
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

The age of sequencing has provided unprecedented insights into the human genome. The coding region of the genome comprises nearly 20,000 genes, of which approximately 4000 are associated with human disease. Beyond the protein-coding genome, which accounts for only 3% of the genome, lies a vast pool of regulatory elements in the form of promoters, enhancers, RNA species, and other intricate elements. These features undoubtably influence human health and disease, and as a result, a great deal of effort is currently being invested in deciphering their identity and mechanism. While a paucity of material has caused a lag in identifying these elements in the inner ear, the emergence of technologies for dealing with a minimal number of cells now has the field working overtime to catch up. Studies on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), methylation, histone modifications, and more are ongoing. A number of microRNAs and other noncoding elements are known to be associated with hearing impairment and there is promise that regulatory elements will serve as future tools and targets of therapeutics and diagnostics. This review covers the current state of the field and considers future directions for the noncoding genome and implications for hearing loss.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and material

Not applicable.

Code availability

Not applicable.

References

  • Abu Rayyan A, Kamal L, Casadei S et al (2020) Genomic analysis of inherited hearing loss in the Palestinian population. Proc Natl Acad Sci USA 117:20070–20076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bademci G, Abad C, Cengiz FB et al (2020) Long-range cis-regulatory elements controlling GDF6 expression are essential for ear development. J Clin Invest 130:4213–4217

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bahloul A, Simmler MC, Michel V et al (2009) Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells. EMBO Mol Med 1:125–138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beermann J, Piccoli MT, Viereck J, Thum T (2016) Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev 96:1297–1325

    Article  CAS  PubMed  Google Scholar 

  • Bermingham NA, Hassan BA, Price SD et al (1999) Math1: an essential gene for the generation of inner ear hair cells. Science 284:1837–1841

    Article  CAS  PubMed  Google Scholar 

  • Bitner-Glindzicz M, Turnpenny P, Hoglund P et al (1995) Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3. Hum Mol Genet 4:1467–1469

    Article  CAS  PubMed  Google Scholar 

  • Bohnsack MT, Czaplinski K, Gorlich D (2004) Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 10:185–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brownstein Z, Gulsuner S, Walsh T et al (2020) Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1. Clin Genet 98:353–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cabili MN, Trapnell C, Goff L et al (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25:1915–1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cabili MN, Dunagin MC, McClanahan PD et al (2015) Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution. Genome Biol 16:20

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Camargo AP, Nakahara TS, Firmino LER et al (2019) Uncovering the mouse olfactory long non-coding transcriptome with a novel machine-learning model. DNA Res 26:365–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136:642–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chipman LB, Pasquinelli AE (2019) miRNA targeting: growing beyond the seed. Trends Genet 35:215–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conte I, Banfi S, Bovolenta P (2013) Non-coding RNAs in the development of sensory organs and related diseases. Cell Mol Life Sci 70:4141–4155

    Article  CAS  PubMed  Google Scholar 

  • Cooper GM, Stone EA, Asimenos G et al (2005) Distribution and intensity of constraint in mammalian genomic sequence. Genome Res 15:901–913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coppola CJ, Ramaker RC, Mendenhall EM (2016) Identification and function of enhancers in the human genome. Hum Mol Genet 25:R190–R197

    Article  CAS  PubMed  Google Scholar 

  • Dahl JA, Collas P (2009) MicroChIP: chromatin immunoprecipitation for small cell numbers. Methods Mol Biol 567:59–74

    Article  CAS  PubMed  Google Scholar 

  • Daniel B, Nagy G, Nagy L (2014) The intriguing complexities of mammalian gene regulation: how to link enhancers to regulated genes. Are we there yet? FEBS Lett 588:2379–2391

    Article  CAS  PubMed  Google Scholar 

  • Davoudi-Dehaghani E, Zeinali S, Mahdieh N et al (2013) A transversion mutation in non-coding exon 3 of the TMC1 gene in two ethnically related Iranian deaf families from different geographical regions; evidence for founder effect. Int J Pediatr Otorhinolaryngol 77:821–826

    Article  PubMed  Google Scholar 

  • de Kok YJ, Merkx GF, van der Maarel SM et al (1995) A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene. Hum Mol Genet 4:2145–2150

    Article  PubMed  Google Scholar 

  • de Kok YJ, Cremers CW, Ropers HH, Cremers FP (1997) The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation. Hum Mutat 10:207–211

    Article  PubMed  Google Scholar 

  • Delmaghani S, El-Amraoui A (2020) Inner ear gene therapies take off: current promises and future challenges. J Clin Med 9:2309

    Article  CAS  PubMed Central  Google Scholar 

  • Derrien T, Johnson R, Bussotti G et al (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–1789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du J, Zhang X, Cao H et al (2017) MiR-194 is involved in morphogenesis of spiral ganglion neurons in inner ear by rearranging actin cytoskeleton via targeting RhoB. Int J Dev Neurosci 63:16–26

    Article  CAS  PubMed  Google Scholar 

  • ENCODE Project Consortium, Snyder MP, Gingeras TR et al (2020) Perspectives on ENCODE. Nature 583:693–698

  • Estivill X, Fortina P, Surrey S et al (1998) Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet 351:394–398

    Article  CAS  PubMed  Google Scholar 

  • Evsen L, Li X, Zhang S et al (2020) let-7 miRNAs inhibit CHD7 expression and control auditory-sensory progenitor cell behavior in the developing inner ear. Development 147:dev183384

  • Faghihi MA, Modarresi F, Khalil AM et al (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 14:723–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan Y, Zhang Y, Wu R et al (2016) miR-431 is involved in regulating cochlear function by targeting Eya4. Biochim Biophys Acta 1862:2119–2126

    Article  CAS  PubMed  Google Scholar 

  • Fan J, Jia L, Li Y et al (2017) Maturation arrest in early postnatal sensory receptors by deletion of the miR-183/96/182 cluster in mouse. Proc Natl Acad Sci USA 114:E4271–E4280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friedman TB, Griffith AJ (2003) Human nonsyndromic sensorineural deafness. Annu Rev Genomics Hum Genet 4:341–402

    Article  CAS  PubMed  Google Scholar 

  • Friedman LM, Dror AA, Mor E et al (2009) MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. Proc Natl Acad Sci USA 106:7915–7920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geng R, Furness DN, Muraleedharan CK et al (2018) The microRNA-183/96/182 cluster is essential for stereociliary bundle formation and function of cochlear sensory hair cells. Sci Rep 8:18022

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gnedeva K, Wang X, McGovern MM et al (2020) Organ of Corti size is governed by Yap/Tead-mediated progenitor self-renewal. Proc Natl Acad Sci USA 117:13552–13561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grimsley-Myers CM, Sipe CW, Geleoc GS, Lu X (2009) The small GTPase Rac1 regulates auditory hair cell morphogenesis. J Neurosci 29:15859–15869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Groves AK, Fekete DM (2012) Shaping sound in space: the regulation of inner ear patterning. Development 139:245–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu C, Li X, Tan Q et al (2013) MiR-183 family regulates chloride intracellular channel 5 expression in inner ear hair cells. Toxicol in Vitro 27:486–491

    Article  CAS  PubMed  Google Scholar 

  • Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9:703–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guttman M, Amit I, Garber M et al (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hao QQ, Li L, Chen W et al (2018) Key genes and pathways associated with inner ear malformation in SOX10 (p.R109W) mutation pigs. Front Mol Neurosci 11:181

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Harfe BD (2005) MicroRNAs in vertebrate development. Curr Opin Genet Dev 15:410–415

    Article  CAS  PubMed  Google Scholar 

  • He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531

    Article  CAS  PubMed  Google Scholar 

  • Helms AW, Abney AL, Ben-Arie N et al (2000) Autoregulation and multiple enhancers control Math1 expression in the developing nervous system. Development 127:1185–1196

    Article  CAS  PubMed  Google Scholar 

  • Hu W, Alvarez-Dominguez JR, Lodish HF (2012) Regulation of mammalian cell differentiation by long non-coding RNAs. EMBO Rep 13:971–983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huyghe A, Van den Ackerveken P, Sacheli R et al (2015) MicroRNA-124 regulates cell specification in the cochlea through modulation of Sfrp4/5. Cell Rep 13:31–42

    Article  CAS  PubMed  Google Scholar 

  • Issler O, van der Zee YY, Ramakrishnan A et al (2020) Sex-specific role for the long non-coding RNA LINC00473 in depression. Neuron 106:912–926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jen HI, Hill MC, Tao L et al (2019) Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1. Elife 8:e44328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji P, Diederichs S, Wang W et al (2003) MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22:8031–8041

    Article  PubMed  CAS  Google Scholar 

  • Jiang W, Peng A, Chen Y et al (2020) Long noncoding RNA EBLN3P promotes the recovery of the function of impaired spiral ganglion neurons by competitively binding to miR2045p and regulating TMPRSS3 expression. Int J Mol Med 45:1851–1863

    CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson KR, Gagnon LH, Tian C et al (2018) Deletion of a long-range Dlx5 enhancer disrupts inner ear development in mice. Genetics 208:1165–1179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karali M, Banfi S (2019) Non-coding RNAs in retinal development and function. Hum Genet 138:957–971

    Article  CAS  PubMed  Google Scholar 

  • Kaya-Okur HS, Wu SJ, Codomo CA et al (2019) CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat Commun 10:1930

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kelley MW (2006) Regulation of cell fate in the sensory epithelia of the inner ear. Nat Rev Neurosci 7:837–849

    Article  CAS  PubMed  Google Scholar 

  • Kelly M, Chen P (2007) Shaping the mammalian auditory sensory organ by the planar cell polarity pathway. Int J Dev Biol 51:535–547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan AO, Becirovic E, Betz C et al (2017) A deep intronic CLRN1 (USH3A) founder mutation generates an aberrant exon and underlies severe Usher syndrome on the Arabian Peninsula. Sci Rep 7:1411

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kiang DT, Jin N, Tu ZJ, Lin HH (1997) Upstream genomic sequence of the human connexin26 gene. Gene 199:165–171

    Article  CAS  PubMed  Google Scholar 

  • Kiernan AE, Pelling AL, Leung KK et al (2005) Sox2 is required for sensory organ development in the mammalian inner ear. Nature 434:1031–1035

    Article  CAS  PubMed  Google Scholar 

  • Koffler-Brill T, Taiber S, Anaya A et al (2020) Identification and characterization of key long non-coding RNAs in the mouse cochlea. RNA Biol 18:1160–1169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kopp F, Mendell JT (2018) Functional classification and experimental dissection of long noncoding RNAs. Cell 172:393–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kung JT, Colognori D, Lee JT (2013) Long noncoding RNAs: past, present, and future. Genetics 193:651–669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis MA, Quint E, Glazier AM et al (2009) An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat Genet 41:614–618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis MA, Di Domenico F, Ingham NJ et al (2020) Hearing impairment due to Mir183/96/182 mutations suggests both loss and gain of function effects. Dis Model Mech 14:dmm047225.

  • Lezirovitz K, Vieira-Silva GA, Batissoco AC et al (2020) A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58. Hum Mol Genet 29:1520–1536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Q, Chen Y, Kubota F et al (2010) Expression of protocadherin-19 in the nervous system of the embryonic zebrafish. Int J Dev Biol 54:905–911

    Article  CAS  PubMed  Google Scholar 

  • Manji SS, Sorensen BS, Klockars T et al (2006) Molecular characterization and expression of maternally expressed gene 3 (Meg3/Gtl2) RNA in the mouse inner ear. J Neurosci Res 83:181–190

    Article  CAS  PubMed  Google Scholar 

  • Matharu N, Rattanasopha S, Tamura S et al (2019) CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. Science 363:eaau0629

  • Matos TD, Simoes-Teixeira H, Caria H et al (2011) Assessing noncoding sequence variants of GJB2 for hearing loss association. Genet Res Int 2011:827469

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mencia A, Modamio-Hoybjor S, Redshaw N et al (2009) Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat Genet 41:609–613

    Article  CAS  PubMed  Google Scholar 

  • Morell RJ, Olszewski R, Tona R et al (2020) Noncoding microdeletion in mouse Hgf disrupts neural crest migration into the stria vascularis, reduces the endocochlear potential, and suggests the neuropathology for human nonsyndromic deafness DFNB39. J Neurosci 40:2976–2992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morsli H, Choo D, Ryan A et al (1998) Development of the mouse inner ear and origin of its sensory organs. J Neurosci 18:3327–3335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naranjo S, Voesenek K, de la Calle-Mustienes E et al (2010) Multiple enhancers located in a 1-Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearing. Hum Genet 128:411–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olusanya BO, Davis AC, Hoffman HJ (2019) Hearing loss: rising prevalence and impact. Bull World Health Organ 97:646-646A

    Article  PubMed  Google Scholar 

  • Pasmant E, Sabbagh A, Vidaud M, Bieche I (2011) ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J 25:444–448

    Article  CAS  PubMed  Google Scholar 

  • Piletic K, Kunej T (2016) MicroRNA epigenetic signatures in human disease. Arch Toxicol 90:2405–2419

    Article  CAS  PubMed  Google Scholar 

  • Pollard KS, Hubisz MJ, Rosenbloom KR, Siepel A (2010) Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res 20:110–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reardon S (2021) A complete human genome sequence is close: how scientists filled in the gaps. Nature 594:158–159

  • Rehman AU, Morell RJ, Belyantseva IA et al (2010) Targeted capture and next-generation sequencing identifies C9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness DFNB79. Am J Hum Genet 86:378–388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riccardi S, Bergling S, Sigoillot F et al (2016) MiR-210 promotes sensory hair cell formation in the organ of corti. BMC Genomics 17:309

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Roberts KA, Abraira VE, Tucker AF et al (2012) Mutation of Rubie, a novel long non-coding RNA located upstream of Bmp4, causes vestibular malformation in mice. PLoS ONE 7:e29495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rudnicki A, Isakov O, Ushakov K et al (2014) Next-generation sequencing of small RNAs from inner ear sensory epithelium identifies microRNAs and defines regulatory pathways. BMC Genomics 15:484

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sacheli R, Nguyen L, Borgs L et al (2009) Expression patterns of miR-96, miR-182 and miR-183 in the development inner ear. Gene Expr Patterns 9:364–370

    Article  CAS  PubMed  Google Scholar 

  • Sallam T, Sandhu J, Tontonoz P (2018) Long noncoding RNA discovery in cardiovascular disease: decoding form to function. Circ Res 122:155–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaffner W (2015) Enhancers, enhancers—from their discovery to today’s universe of transcription enhancers. Biol Chem 396:311–327

    Article  CAS  PubMed  Google Scholar 

  • Schaub MA, Boyle AP, Kundaje A et al (2012) Linking disease associations with regulatory information in the human genome. Genome Res 22:1748–1759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schilder AGM, Su MP, Blackshaw H et al (2019) Hearing protection, restoration, and regeneration: an overview of emerging therapeutics for inner ear and central hearing disorders. Otol Neurotol 40:559–570

    Article  PubMed  Google Scholar 

  • Schmitt AM, Chang HY (2016) Long noncoding RNAs in cancer pathways. Cancer Cell 29:452–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schrauwen I, Hasin-Brumshtein Y, Corneveaux JJ et al (2016) A comprehensive catalogue of the coding and non-coding transcripts of the human inner ear. Hear Res 333:266–274

    Article  CAS  PubMed  Google Scholar 

  • Schultz JM, Khan SN, Ahmed ZM et al (2009) Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39. Am J Hum Genet 85:25–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shahin H, Walsh T, Sobe T et al (2002) Genetics of congenital deafness in the Palestinian population: multiple connexin 26 alleles with shared origins in the Middle East. Hum Genet 110:284–289

    Article  CAS  PubMed  Google Scholar 

  • Shearer AE, Smith RJ (2012) Genetics: advances in genetic testing for deafness. Curr Opin Pediatr 24:679–686

    Article  PubMed  PubMed Central  Google Scholar 

  • Shearer AE, Smith RJ (2015) Massively parallel sequencing for genetic diagnosis of hearing loss: the new standard of care. Otolaryngol Head Neck Surg 153:175–182

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi X, Sun M, Liu H et al (2013) Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett 339:159–166

    Article  CAS  PubMed  Google Scholar 

  • Siepel A, Haussler D (2004) Computational identification of evolutionarily conserved exons. In: RECOMB 04', pp 177–186

  • Siepel A, Bejerano G, Pedersen JS et al (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15:1034–1050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skene PJ, Henikoff JG, Henikoff S (2018) Targeted in situ genome-wide profiling with high efficiency for low cell numbers. Nat Protoc 13:1006–1019

    Article  CAS  PubMed  Google Scholar 

  • Soukup GA, Fritzsch B, Pierce ML et al (2009) Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice. Dev Biol 328:328–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stojanova ZP, Kwan T, Segil N (2015) Epigenetic regulation of Atoh1 guides hair cell development in the mammalian cochlea. Development 142:3529–3536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turner TN, Eichler EE (2019) The role of de novo noncoding regulatory mutations in neurodevelopmental disorders. Trends Neurosci 42:115–127

    Article  CAS  PubMed  Google Scholar 

  • Ulitsky I, Bartel DP (2013) lincRNAs: Genomics, evolution, and mechanisms. Cell 154:26–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ushakov K, Koffler-Brill T, Aviv R et al (2017) Genome-wide identification and expression profiling of long non-coding RNAs in auditory and vestibular systems. Sci Rep 7:8637

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Van den Ackerveken P, Mounier A, Huyghe A et al (2017) The miR-183/ItgA3 axis is a key regulator of prosensory area during early inner ear development. Cell Death Differ 24:2054–2065

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vissers LE, van Ravenswaaij CM, Admiraal R et al (2004) Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet 36:955–957

    Article  CAS  PubMed  Google Scholar 

  • Wallis D, Hamblen M, Zhou Y et al (2003) The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development 130:221–232

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Liu W, Jiao J et al (2017) Expression profiling of mRNAs and long non-coding RNAs in aged mouse olfactory bulb. Sci Rep 7:2079

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang C, Yu G, Xu Y et al (2021) Knockdown of long non-coding RNA HCP5 increases radiosensitivity through cellular senescence by regulating microRNA-128 in gliomas. Cancer Manage Res 13:3723–3737

    Article  CAS  Google Scholar 

  • Watson CJ, Lies SM, Minich RR, Tempel BL (2014) Changes in cochlear PMCA2 expression correlate with the maturation of auditory sensitivity. J Assoc Res Otolaryngol 15:543–554

    Article  PubMed  PubMed Central  Google Scholar 

  • Wayne S, Robertson NG, DeClau F et al (2001) Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Hum Mol Genet 10:195–200

    Article  CAS  PubMed  Google Scholar 

  • Weston MD, Pierce ML, Rocha-Sanchez S et al (2006) MicroRNA gene expression in the mouse inner ear. Brain Res 1111:95–104

    Article  CAS  PubMed  Google Scholar 

  • Weston MD, Pierce ML, Jensen-Smith HC et al (2011) MicroRNA-183 family expression in hair cell development and requirement of microRNAs for hair cell maintenance and survival. Dev Dyn 240:808–819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilch E, Azaiez H, Fisher RA et al (2010) A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression. Clin Genet 78:267–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiang M, Gan L, Li D et al (1997) Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development. Proc Natl Acad Sci USA 94:9445–9450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong W, Wu DM, Xue Y et al (2019) AAV cis-regulatory sequences are correlated with ocular toxicity. Proc Natl Acad Sci USA 116:5785–5794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yarani R, Mirza AH, Kaur S, Pociot F (2018) The emerging role of lncRNAs in inflammatory bowel disease. Exp Mol Med 50:1–14

    Article  PubMed  CAS  Google Scholar 

  • Yizhar-Barnea O, Valensisi C, Jayavelu ND et al (2018) DNA methylation dynamics during embryonic development and postnatal maturation of the mouse auditory sensory epithelium. Sci Rep 8:17348

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yoshimura H, Shibata SB, Ranum PT et al (2019) Targeted allele suppression prevents progressive hearing loss in the mature murine model of human TMC1 deafness. Mol Ther 27:681–690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young TL, Matsuda T, Cepko CL (2005) The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol 15:501–512

    Article  CAS  PubMed  Google Scholar 

  • Yu Y, Liao L, Shao B et al (2017) Knockdown of microRNA Let-7a improves the functionality of bone marrow-derived mesenchymal stem cells in immunotherapy. Mol Ther 25:480–493

    Article  CAS  PubMed  Google Scholar 

  • Zheng W, Huang L, Wei ZB et al (2003) The role of Six1 in mammalian auditory system development. Development 130:3989–4000

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

K.B.A. is an incumbent of the Drs. Sarah and Felix Dumont Chair for Research of Hearing Disorders.

Funding

Research in the Avraham laboratory on hearing is funded by the National Institutes of Health/NIDCD R01DC011835; the United States-Israel Binational Science Foundation (BSF) 01027150, Jerusalem, Israel; the Israel Science Foundation (grant No. 1763/20); the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine (K.B.A.); the German-Israeli Foundation for Scientific Research and Development Agreement No. I-1430–415.13/2017; the Israel Science Foundation within the Israel Precision Medicine Partnership Program, Grant/Award Number: 3499/19; and the Klass Family.

Author information

Authors and Affiliations

  1. Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, 6997801, Tel Aviv, Israel

    Karen B. Avraham, Lama Khalaily, Yael Noy, Lara Kamal, Tal Koffler-Brill & Shahar Taiber

Authors
  1. Karen B. Avraham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lama Khalaily
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yael Noy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lara Kamal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tal Koffler-Brill
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shahar Taiber
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors participated in the writing and read and approved the final version.

Corresponding author

Correspondence to Karen B. Avraham.

Ethics declarations

Conflict of interest

None.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Avraham, K.B., Khalaily, L., Noy, Y. et al. The noncoding genome and hearing loss. Hum Genet 141, 323–333 (2022). https://doi.org/10.1007/s00439-021-02359-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-021-02359-z

Search

Navigation