Jankowsky Eckhard, Guenther Ulf-Peter
Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
EMBL, Heidelberg, Germany.
Curr Genet. 2019 Apr;65(2):453-456. doi: 10.1007/s00294-018-0911-z. Epub 2018 Nov 27.
Upstream open reading frames (uORFs) in 5' UTRs of eukaryotic mRNAs are increasingly recognized as important elements that regulate cellular protein synthesis. Since uORFs can start from non-AUG codons, an enormous number of potential uORF initiation sites exists in 5'UTRs. However, only a subset of these sites is used and it has been unclear how actual start sites are selected. Studies of the DEAD-box helicase Ded1p from S. cerevisiae show that translation of uORFs with non-AUG initiation codons occurs upstream of mRNA structures that emerge with defective Ded1p. The data designate mRNA structure as important determinant for non-AUG initiation sites of uORFs. Ded1p can control this RNA structure and thereby regulate uORF translation.
真核生物mRNA 5'非翻译区(UTR)中的上游开放阅读框(uORF)越来越被认为是调节细胞蛋白质合成的重要元件。由于uORF可以从非AUG密码子起始,5'UTR中存在大量潜在的uORF起始位点。然而,这些位点中只有一部分被使用,目前尚不清楚实际的起始位点是如何被选择的。对酿酒酵母中DEAD盒解旋酶Ded1p的研究表明,具有非AUG起始密码子的uORF的翻译发生在因Ded1p缺陷而出现的mRNA结构的上游。这些数据表明mRNA结构是uORF非AUG起始位点的重要决定因素。Ded1p可以控制这种RNA结构,从而调节uORF的翻译。