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

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.