Analysis of small human proteins reveals the translation of upstream open reading frames of mRNAs.
To find novel short coding sequences from accumulated full-length cDNA sequences, proteomic analysis of small proteins expressed in human leukemia K562 cells was performed using high-resolution nanoflow liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Our analysis led to the identification of 54 proteins not more than 100 amino acids in length, including four novel ones. These novel short coding sequences were all located upstream of the longest open reading frame (ORF) of the corresponding cDNA. Our findings indicate that the translation of short ORFs occurs in vivo whether or not there exists a longer coding region in the downstream of the mRNA. This investigation provides the first direct evidence of translation of upstream ORFs in human cells, which could greatly change the current outline of the human proteome.
Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Masaaki
M
Oyama
Chiharu
C
Itagaki
Hiroko
H
Hata
Yutaka
Y
Suzuki
Tomonori
T
Izumi
Tohru
T
Natsume
Toshiaki
T
Isobe
Sumio
S
Sugano
D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics*; D014176:Protein Biosynthesis; D020543:Proteome; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D020543:Proteome; D012333:RNA, Messenger