A hidden human proteome encoded by ‘non-coding’ genes

Abstract

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/or parallel reaction monitoring (PRM); and 10 new proteins 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.

Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA

“…The protein UBAP1-AST6 is translated from a lncRNA, is localized mainly to the nucleus, and is expressed in A549 lung cancer cells. UBAP1-AST6 promotes cancer, and its overexpression significantly induces cancer cell proliferation and colony formation [173] (Fig. 1f).…”

Long Non-coding Wilms Tumor 1 Antisense RNA in the Development and Progression of Malignant Tumors

“…Interestingly, Anderson et al reported that the lncRNA LINC00948 could serve as templates for the translation of functional micropeptides myoregulin (MLN), and MLN was an essential regulator of skeletal muscle activities (9). Similarly, Lu et al reported the same function of lncRNA and detected 308 lncRNA-encoded new peptides according to shotgun proteomics (10). Those results indicate that lncRNAs are complex and versatile regulators that may be involved in many biological processes.…”

LncRNA FGD5‐AS1 can be predicted as therapeutic target in oral cancer

“…Long non‐coding RNAs (lncRNAs) are those genes longer than 200 nucleotides (nt) in length but without the ability to encode proteins . LncRNAs have been reported to be aberrantly expressed in many diseases, including cancer, and plays a vital role in tumor growth and progression .…”

“…Long non-coding RNAs (lncRNAs) are those genes longer than 200 nucleotides (nt) in length but without the ability to encode proteins. 4 LncRNAs have been reported to be aberrantly expressed in many diseases, including cancer, and plays a vital role in tumor growth and progression. [5][6][7][8] Furthermore, lncRNAs have been discovered to be participated in various biological and pathological activities, such as cell growth, apoptosis, invasion, and migration.…”