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RNA结合蛋白Rbm24a及其靶点在小眼症中的功能作用

Functional Role of the RNA-Binding Protein Rbm24a and Its Target in Microphthalmia.

作者信息

Brastrom Lindy K, Scott C Anthony, Wang Kai, Slusarski Diane C

机构信息

Department of Biology, University of Iowa, Iowa City, IA 52245, USA.

Mercury Data Science, Houston, TX 77098, USA.

出版信息

Biomedicines. 2021 Jan 21;9(2):100. doi: 10.3390/biomedicines9020100.

DOI:10.3390/biomedicines9020100
PMID:33494192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7909789/
Abstract

Congenital eye defects represent a large class of disorders affecting roughly 21 million children worldwide. Microphthalmia and anophthalmia are relatively common congenital defects, with approximately 20% of human cases caused by mutations in Recently, we identified the RNA-binding motif protein 24a (Rbm24a) which binds to and regulates in zebrafish and mice. Here we show that morpholino knockdown of leads to microphthalmia and visual impairment. By utilizing sequential injections, we demonstrate that addition of exogenous RNA to -deplete embryos is sufficient to suppress morphological and visual defects. This research demonstrates a critical role for understanding the post-transcriptional regulation of genes needed for development.

摘要

先天性眼缺陷是一大类疾病,全球约有2100万儿童受其影响。小眼症和无眼症是相对常见的先天性缺陷,约20%的人类病例是由 中的突变引起的。最近,我们鉴定出RNA结合基序蛋白24a(Rbm24a),它在斑马鱼和小鼠中与 结合并对其进行调控。在这里,我们表明,通过吗啉代敲低 会导致小眼症和视力损害。通过连续注射,我们证明向 -缺失胚胎中添加外源性RNA足以抑制形态和视觉缺陷。这项研究证明了理解发育所需基因的转录后调控的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/f28a16a87a19/biomedicines-09-00100-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/fe9533b067e6/biomedicines-09-00100-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/5f206e0ca5e5/biomedicines-09-00100-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/73e2c3c21a46/biomedicines-09-00100-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/fd9945874041/biomedicines-09-00100-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/46615602b9a6/biomedicines-09-00100-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/ed35fe12da2c/biomedicines-09-00100-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/f28a16a87a19/biomedicines-09-00100-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/fe9533b067e6/biomedicines-09-00100-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/5f206e0ca5e5/biomedicines-09-00100-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/73e2c3c21a46/biomedicines-09-00100-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/fd9945874041/biomedicines-09-00100-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/46615602b9a6/biomedicines-09-00100-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/ed35fe12da2c/biomedicines-09-00100-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3f/7909789/f28a16a87a19/biomedicines-09-00100-g007.jpg

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本文引用的文献

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Rbm24 controls poly(A) tail length and translation efficiency of mRNAs in the lens via cytoplasmic polyadenylation.Rbm24 通过细胞质聚腺苷酸化控制晶状体中 mRNAs 的多聚 (A) 尾长和翻译效率。
Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7245-7254. doi: 10.1073/pnas.1917922117. Epub 2020 Mar 13.
2
The master transcription factor SOX2, mutated in anophthalmia/microphthalmia, is post-transcriptionally regulated by the conserved RNA-binding protein RBM24 in vertebrate eye development.主转录因子 SOX2 在无眼症/小眼症中发生突变,在脊椎动物眼睛发育过程中受保守 RNA 结合蛋白 RBM24 的转录后调控。
Hum Mol Genet. 2020 Mar 13;29(4):591-604. doi: 10.1093/hmg/ddz278.
3
A High-Throughput Assay for Congenital and Age-Related Eye Diseases in Zebrafish.
一种用于斑马鱼先天性和年龄相关性眼病的高通量检测方法。
Biomedicines. 2019 Apr 11;7(2):28. doi: 10.3390/biomedicines7020028.
4
RNA binding protein 24 deletion disrupts global alternative splicing and causes dilated cardiomyopathy.RNA 结合蛋白 24 缺失破坏全局选择性剪接并导致扩张型心肌病。
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A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells.一种高保真 Cas9 突变体作为核糖核蛋白复合物递送至体内,可实现人类造血干细胞和祖细胞中的高效基因编辑。
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