Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation.
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.
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Ariel A
AA
Bazzini
Timothy G
TG
Johnstone
Romain
R
Christiano
Sebastian D
SD
Mackowiak
Benedikt
B
Obermayer
Elizabeth S
ES
Fleming
Charles E
CE
Vejnar
Miler T
MT
Lee
Nikolaus
N
Rajewsky
Tobias C
TC
Walther
Antonio J
AJ
Giraldez
D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D006801:Humans; D008969:Molecular Sequence Data; D023282:Nuclease Protection Assays; D009842:Oligopeptides / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D017423:Sequence Analysis, RNA / Q000379:methods; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*
D009842:Oligopeptides; D012333:RNA, Messenger