Translation of small downstream ORFs enhances translation of canonical main open reading frames

Translation of small downstream ORFs enhances translation of canonical main open reading frames
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DOI:
10.15252/embj.2020104763
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发表时间:
2020-08-03
期刊:
影响因子:
11.4
通讯作者:
Bazzini, Ariel A.
Bazzini, Ariel A.
中科院分区:
生物学1区
文献类型:
--
作者:
Wu, Qiushuang;Wright, Matthew;Bazzini, Ariel A.

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除了典型的开放阅读框架(ORF)之外,在真核生物的非翻译mRNA区域(UTR)中已经鉴定了数千个翻译的小ORF(含有少于100个密码子)。5 'UTR中的小ORF(上游(u)ORF)通常抑制相同mRNA内的典型ORF的翻译。然而,3 'UTR中翻译的小ORF(下游(d)ORF)的功能是未知的。与uORF相反,我们发现dORF的翻译增强了其相应的规范ORF的翻译。dORF的这种翻译刺激作用取决于dORF的数量,而不是它们编码的长度或肽。我们认为dORF代表了脊椎动物中一种新的、强有力的、通用的翻译调控机制。
In addition to canonical open reading frames (ORFs), thousands of translated small ORFs (containing less than 100 codons) have been identified in untranslated mRNA regions (UTRs) across eukaryotes. Small ORFs in 5 ' UTRs (upstream (u)ORFs) often repress translation of the canonical ORF within the same mRNA. However, the function of translated small ORFs in the 3 ' UTRs (downstream (d)ORFs) is unknown. Contrary to uORFs, we find that translation of dORFs enhances translation of their corresponding canonical ORFs. This translation stimulatory effect of dORFs depends on the number of dORFs, but not the length or peptide they encode. We propose that dORFs represent a new, strong, and universal translation regulatory mechanism in vertebrates.