کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
1904453 1534628 2016 8 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
miR-431 is involved in regulating cochlear function by targeting Eya4
ترجمه فارسی عنوان
miR-431 در تنظیم عملکرد حلزون با هدف قرار دادن Eya4 دخالت دارد
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کلمات کلیدی
miR-431؛ Eya4؛ موس تراریخته؛ Cochleae؛ نورون های اسپیرال گانگلیون
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی


• miR-431 Tg mice exhibit hearing loss.
• SGN density is lower in cochleae of miR-431 Tg mice compared with Wt mice.
• SGNs in cultures from Tg mice are less numerous and their neurites are shorter.
• miR-431 directly targets Eya4 mRNA to regulate cochlear function.

To understand the relationship between microRNAs and hearing loss and help clarify the causes of hereditary deafness, we studied the functions of miR-431 in cochleae. We first investigated the spatial-temporal expression profiles of miR-431 in spiral ganglion neurons (SGNs) in cochleae using real-time PCR and miRNA in situ hybridization. These studies showed that expression of miR-431 was high in SGNs in the cochleae of newborn mice, and decreased as development progressed. To test the functional effects of miR-431, we established miR-431 overexpressing transgenic (Tg) mice. Surface preparations of the cochlear basilar membrane and cochlear sections revealed no major structural differences between Tg and wild-type (Wt) mice. However, a comparison of auditory brain stem responses (ABRs) in Tg and Wt mice showed that ABR thresholds were significantly higher in Tg mice than in Wt mice. Notably, the density of SGNs was significantly lower in Tg mice than in Wt mice. We also found that the proportion of mature SGNs in cultures of primary SGNs from Tg cochleae was lower and their axons were shorter. A bioinformatics analysis predicted that the mRNA target of miR-431 was Eya4, a finding confirmed by luciferase reporter assays and western blotting. Importantly, overexpression of miR-431 in cochleae of Tg mice inhibited the translation of Eya4 mRNA, leading to a deficiency of EYA4. Thus, excessive amounts of miR-431 in cochleae of Tg mice may be the cause of sparse SGNs, which in turn could be responsible for hearing loss.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 11, November 2016, Pages 2119–2126
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