Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss
Abstract
MicroRNAs (miRNAs) bind to complementary sites in their target mRNAs to mediate post-transcriptional repression, with the specificity of target recognition being crucially dependent on the miRNA seed region. Impaired miRNA target binding resulting from SNPs within mRNA target sites has been shown to lead to pathologies associated with dysregulated gene expression. However, no pathogenic mutations within the mature sequence of a miRNA have been reported so far. Here we show that point mutations in the seed region of miR-96, a miRNA expressed in hair cells of the inner ear, result in autosomal dominant, progressive hearing loss. This is the first study implicating a miRNA in a mendelian disorder. The identified mutations have a strong impact on miR-96 biogenesis and result in a significant reduction of mRNA targeting. We propose that these mutations alter the regulatory role of miR-96 in maintaining gene expression profiles in hair cells required for their normal function.
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Point mutations within the seed region of miR-96 cause autosomal dominant non-syndromic sensorineural hearing loss in two Spanish families and in a mouse model of NSHL.
“Recently, point mutations within the seed region of miR-96 were reported in two Spanish families with autosomal dominant non-syndromic sensorineural hearing loss (NSHL) and in a mouse model of NSHL.”
From A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing (2012) · cites this paper as [14]
The MIR96 mutation reported here is the third mutation described in this gene in humans and the first in a population different from that of the original report.
“This is the third mutation described in this gene in humans, and the first in a different population from that of the original report (14).”
From A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing (2012) · cites this paper as [14]
Mutations within miR-96 are not a common cause of deafness.
“Even though mutations within miR-96 are not a common cause of deafness, as evidenced by this and previous works (14,17), the description of novel causative variants might help in elucidating the pathogenic mechanisms underlying the DFNA50-associated phenotype.”
From A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing (2012) · cites this paper as [14]
Heterozygous loss-of-function point mutations of miRNA genes are associated with several human congenital disorders.
“Heterozygous loss-of-function point mutations of miRNA genes are associated with several human congenital disorders1–5”
From Gain-of-function mutation of microRNA-140 in human skeletal dysplasia (2019) · cites this paper as [1]
Besides gene dosage abnormalities, single nucleotide substitutions in two miRNA genes have been identified in human diseases: MIR96 mutations in autosomal dominant deafness 50 and MIR184 mutations in EDICT syndrome and familial and sporadic cases of keratoconus.
“Besides gene dosage abnormalities37,38, single nucleotide substitutions in two miRNA genes have been identified in human diseases: MIR96 mutations in autosomal dominant deafness 50 (#613704) and MIR184 mutations in EDICT syndrome (#614303) and familial and sporadic cases of keratoconus1–5,39.”
From Gain-of-function mutation of microRNA-140 in human skeletal dysplasia (2019) · cites this paper as [1]
Cites
Mfold web server for nucleic acid folding and hybridization prediction
Zuker, M. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg595 · Cited by 13,404 · see citing works
The role of site accessibility in microRNA target recognition
Kertesz, M., Iovino, N., Unnerstall, U., Gaul, U., & Segal, E. (2007) · Nature Genetics · doi:10.1038/ng2135 · Cited by 2,460 · see citing works
Clop, A., Marcq, F., Takeda, H., Pirottin, D., Tordoir, X., Bibé, B., Bouix, J., Caiment, F., Elsen, J.-M., Eychenne, F., et al. (2006) · Nature Genetics · doi:10.1038/ng1810 · Cited by 1,260 · see citing works
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The role of microRNAs in human diseases
Tüfekci, K. U., Öner, M. G., Meuwissen, R. L. J., & Genç, Ş. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-748-8_3 · Cited by 566 · see citing works
Genetic, environmental, and epigenetic factors involved in CAKUT
Nicolaou, N., Renkema, K. Y., Bongers, E. M. H. F., Giles, R. H., & Knoers, N. V. A. M. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.140 · Cited by 344 · see citing works
MicroRNAs and developmental timing
Ambros, V. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2011.04.003 · Cited by 314 · see citing works
Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract
Hughes, A. E., Bradley, D. T., Campbell, M., Lechner, J., Dash, D. P., Simpson, D. A., & Willoughby, C. E. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.09.014 · Cited by 276 · see citing works
Willemsen, M. H., Vallès, A., Kirkels, L. A. M. H., Mastebroek, M., Olde Loohuis, N., Kos, A., Wissink-Lindhout, W. M., de Brouwer, A. P. M., Nillesen, W. M., Pfundt, R., et al. (2011) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2011-100294 · Cited by 202 · see citing works
MicroRNA-183 family members regulate sensorineural fates in the inner ear
Li, H., Kloosterman, W., & Fekete, D. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4948-09.2010 · Cited by 140 · see citing works
miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells
Kuhn, S., Johnson, S. L., Furness, D. N., Chen, J., Ingham, N., Hilton, J. M., Steffes, G., Lewis, M. A., Zampini, V., Hackney, C. M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016646108 · Cited by 114 · see citing works
Self-citationGain-of-function mutation of microRNA-140 in human skeletal dysplasia
Grigelioniene, G., Suzuki, H. I., Taylan, F., Mirzamohammadi, F., Borochowitz, Z. U., Ayturk, U. M., Tzur, S., Horemuzova, E., Lindstrand, A., Weis, M. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0353-2 · Cited by 103 · see citing works
Soldà, G., Robusto, M., Primignani, P., Castorina, P., Benzoni, E., Cesarani, A., Ambrosetti, U., Asselta, R., & Duga, S. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr493 · Cited by 102 · see citing works
Mutational Analysis of <i>MIR184</i> in Sporadic Keratoconus and Myopia
Lechner, J., Bae, H. A., Guduric-Fuchs, J., Rice, A., Govindarajan, G., Siddiqui, S., Abi Farraj, L., Yip, S. P., Yap, M., Das, M., et al. (2013) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.13-12035 · Cited by 78 · see citing works
MiR-182-5p protects inner ear hair cells from cisplatin-induced apoptosis by inhibiting FOXO3a
Li, Y., Li, A., Wu, J., He, Y., Yu, H., Chai, R., & Li, H. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.246 · Cited by 46 · see citing works
miRNA mutations are not a common cause of deafness
Hildebrand, M. S., Witmer, P. D., Xu, S., Newton, S. S., Kahrizi, K., Najmabadi, H., Valle, D., & Smith, R. J. H. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33299 · Cited by 14 · see citing works
- Authors
- Mencía, Á., Modamio-Høybjør, S., Redshaw, N., Morín, M., Mayo-Merino, F., Olavarrieta, L., Aguirre, L. A., del Castillo, I., Steel, K. P., Dalmay, T., Moreno, F., & Moreno-Pelayo, M. Á.
- Affiliations
- Hospital Universitario Ramón y Cajal (ES)
- University of East Anglia (GB)
- Instituto de Salud Carlos III (ES)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Moreno-Pelayo, Miguel Ángel
- ORCID
- Venue
- Nature Genetics
- Published
- 2009-04-12
- Volume
- 41
- Issue
- 5
- Pages
- 609-613
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2091798624
- Cited by
- 550
- References
- 3
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 24 · 2023: 23 · 2022: 25 · 2021: 21 · 2020: 36 · 2019: 32 · 2018: 33 · 2017: 35 · 2016: 30 · 2015: 37 · 2014: 38 · 2013: 54 · 2012: 41
- FWCI
- 22.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Wellcome Trust
- Medical Research Council (MC_qA137918)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Genetics › Congenital Ear and Nasal Anomalies
- Keywords
- miR-96, autosomal dominant inheritance, microRNA biogenesis, hair cells, inner ear, post-transcriptional regulation
- MeSH terms
- Adolescent, Adult, Aged, Base Sequence, Child, Female, Hair Cells, Auditory, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Pedigree, RNA, Messenger, Hearing Loss, MicroRNAs
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