Identification of small ORF s in vertebrates using ribosome footprinting and evolutionary conservation

AA Bazzini, TG Johnstone, R Christiano… - The EMBO …, 2014 - embopress.org
AA Bazzini, TG Johnstone, R Christiano, SD Mackowiak, B Obermayer, ES Fleming…
The EMBO journal, 2014embopress.org
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 …
Abstract
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.
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