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上游开放阅读框：（病理）生理学中的分子开关。

Upstream open reading frames: molecular switches in (patho)physiology.

机构信息

Max Delbrueck Center for Molecular Medicine, Berlin, Germany.

出版信息

Bioessays. 2010 Oct;32(10):885-93. doi: 10.1002/bies.201000037. Epub 2010 Aug 19.

DOI:10.1002/bies.201000037
PMID:20726009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3045505/
Abstract

Conserved upstream open reading frames (uORFs) are found within many eukaryotic transcripts and are known to regulate protein translation. Evidence from genetic and bioinformatic studies implicates disturbed uORF-mediated translational control in the etiology of human diseases. A genetic mouse model has recently provided proof-of-principle support for the physiological relevance of uORF-mediated translational control in mammals. The targeted disruption of the uORF initiation codon within the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) gene resulted in deregulated C/EBPβ protein isoform expression, associated with defective liver regeneration and impaired osteoclast differentiation. The high prevalence of uORFs in the human transcriptome suggests that intensified search for mutations within 5' RNA leader regions may reveal a multitude of alterations affecting uORFs, causing pathogenic deregulation of protein expression.

摘要

上游开放阅读框（uORFs）存在于许多真核生物转录本中，已知其可调节蛋白质翻译。遗传和生物信息学研究的证据表明，uORF 介导的翻译控制失调与人类疾病的病因有关。最近，一种遗传小鼠模型为 uORF 介导的翻译控制在哺乳动物中的生理相关性提供了原理性证据支持。在转录因子 CCAAT/增强子结合蛋白 β（C/EBPβ）基因内靶向破坏 uORF 起始密码子导致 C/EBPβ 蛋白同工型表达失调，与肝再生缺陷和破骨细胞分化受损有关。人类转录组中 uORFs 的高普遍性表明，加强对 5' RNA 前导区突变的搜索可能会揭示出大量影响 uORFs 的改变，导致蛋白质表达的病理性失调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/a9f55d454ad3/bies0032-0885-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/0cd8183ff152/bies0032-0885-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/becc777e0ff6/bies0032-0885-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/85c496eff3a7/bies0032-0885-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/b91876dc057e/bies0032-0885-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/a9f55d454ad3/bies0032-0885-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/0cd8183ff152/bies0032-0885-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/becc777e0ff6/bies0032-0885-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/85c496eff3a7/bies0032-0885-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/b91876dc057e/bies0032-0885-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a44/3045505/a9f55d454ad3/bies0032-0885-f5.jpg

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