Journal
NUCLEIC ACIDS RESEARCH
Volume 47, Issue 15, Pages 8111-8125Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkz646
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Funding
- National Key Research and Development Program of China [2017YFA0505100, 2017YFA0505001, 2018YFC0910202]
- National Basic Research Program '973' of China [2014CBA02000]
- Key Project for Research and Development of Guangdong province [2016B020238002]
- National Natural and Science Foundation of China [81372135, 81322028, 31300649, 31570828]
- Guangdong Key RD Program [2019B020226001]
- National Key Research and Development Program [2017YFA0505100, 2017YFA0505001, 2018YFC0910202]
- National Basic Research Program'973' of China [2014CBA02000]
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It has been a long debate whether the 98% 'noncoding' fraction of human genome can encode functional proteins besides short peptides. With full-length translating mRNA sequencing and ribosome profiling, we found that up to 3330 long non-coding RNAs (lncRNAs) were bound to ribosomes with active translation elongation. With shotgun proteomics, 308 lncRNA-encoded new proteins were detected. A total of 207 unique peptides of these new proteins were verified by multiple reaction monitoring (MRM) and/or parallel reactionmonitoring (PRM); and 10 newproteins were verified by immunoblotting. We found that these new proteins deviated from the canonical proteins with various physical and chemical properties, and emerged mostly in primates during evolution. We further deduced the protein functions by the assays of translation efficiency, RNA folding and intracellular localizations. As the new protein UBAP1-AST6 is localized in the nucleoli and is preferentially expressed by lung cancer cell lines, we biologically verified that it has a function associated with cell proliferation. In sum, we experimentally evidenced a hidden human functional proteome encoded by purported lncRNAs, suggesting a resource for annotating new human proteins.
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