期刊
GENOME RESEARCH
卷 28, 期 1, 页码 25-36出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.226050.117
关键词
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资金
- National Cancer Institute [CA184165]
- NCI's Clinical Proteomic Tumor Analysis Consortium initiative [U24CA210985]
- International Research & Development Program of National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2016K1A3A1A47921601]
- Center for Proteomics Discovery at Johns Hopkins
- [S10OD021844]
- NATIONAL CANCER INSTITUTE [U24CA210985, R01CA184165] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P50AG005146] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD021844] Funding Source: NIH RePORTER
Translation initiation generally occurs at AUG codons in eukaryotes, although it has been shown that non-AUG or non-canonical translation initiation can also occur. However, the evidence for noncanonical translation initiation sites (TISs) is largely indirect and based on ribosome profiling (Ribo-seq) studies. Here, using a strategy specifically designed to enrich N termini of proteins, we demonstrate that many human proteins are translated at noncanonical TISs. The large majority of TISs that mapped to 5' untranslated regions were noncanonical and led to N-terminal extension of annotated proteins or translation of upstream small open reading frames (uORF). It has been controversial whether the amino acid corresponding to the start codon is incorporated at the TIS or methionine is still incorporated. We found that methionine was incorporated at almost all noncanonical TISs identified in this study. Comparison of the TISs determined through mass spectrometry with ribosome profiling data revealed that about two-thirds of the novel annotations were indeed supported by the available ribosome profiling data. Sequence conservation across species and a higher abundance of noncanonical TISs than canonical ones in some cases suggests that the noncanonical TISs can have biological functions. Overall, this study provides evidence of protein translation initiation at noncanonical TISs and argues that further studies are required for elucidation of functional implications of such noncanonical translation initiation.
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