Proteomics

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A Hidden Human Proteome Encoded by the “Non-Coding” Genes


ABSTRACT: It has been a long debate whether the 98% “non-coding” fraction of human genome can encode functional proteins besides a “random noise” of translation. We used our established translatome sequencing (RNC-seq) to analyze human cells and found that up to 3330 long non-coding RNAs (lncRNAs) were bound to ribosomes and thus might be translated into proteins (with more than 50 amino acids). These new protein-coding genes distributed universally in all human chromosomes. We then used various experimental methods including mass spectrometry, immunoblotting, subcellular localization and phenotype assessments to verify the existence of such a hidden human proteome encoded by purported lncRNAs that can express functional proteins. These new proteins deviate from the canonical proteins in various physical and chemical properties, and emerged mostly in primates during evolution. In sum, we experimentally evidenced a hidden human functional proteome encoded by purported lncRNAs, suggesting that the human genome has to be systematically re-annotated.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Yang Wang  

LAB HEAD: Qing-Yu He

PROVIDER: PXD005291 | Pride | 2022-02-25

REPOSITORIES: Pride

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It has been a long debate whether the 98% 'non-coding' 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  ...[more]

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