Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation

Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation
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DOI:
10.1002/embj.201488411
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发表时间:
2014-05-02
期刊:
影响因子:
11.4
通讯作者:
Giraldez, Antonio J.
Giraldez, Antonio J.
中科院分区:
生物学1区
文献类型:
--
作者:
Bazzini, Ariel A.;Johnstone, Timothy G.;Giraldez, Antonio J.

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识别基因组中的编码元件是理解生命系统的基本步骤。短肽(< 100 aa)已成为发育和生理学的重要调节因子,但其鉴定受到其大小的限制。我们利用核糖体在mRNA上运动的周期性,通过核糖体足迹来定义主动翻译的ORF。这种方法在斑马鱼和人类中鉴定了数百个翻译的小ORF。从密码子保守模式的小ORF的计算预测证实并扩展了这些发现,并确定了斑马鱼和人类的保守序列,表明功能性肽产物(微肽)。这些结果确定了脊椎动物中的微肽编码基因,提供了一个切入点,以确定其在体内的功能。
Identification of the coding elements in the genome is a fundamental step to understanding the building blocks of living systems. Short peptides (< 100 aa) have emerged as important regulators of development and physiology, but their identification has been limited by their size. We have leveraged the periodicity of ribosome movement on the mRNA to define actively translated ORFs by ribosome footprinting. This approach identifies several hundred translated small ORFs in zebrafish and human. Computational prediction of small ORFs from codon conservation patterns corroborates and extends these findings and identifies conserved sequences in zebrafish and human, suggesting functional peptide products (micropeptides). These results identify micropeptide-encoding genes in vertebrates, providing an entry point to define their function in vivo.