LncRNAs encoded polypeptides or microproteins were first found enriched in cell culture-derived and circulating extracellular vesicles and of potential diagnostic application
Long noncoding RNAs (lncRNAs) are a family of non-coding RNAs (ncRNAs) exceeding 200 nucleotides in length that were initially considered as "junk RNAs", as they possess no apparent open reading frames (ORFs) for proteins > 100 amino acids (aa). However, advancements in bioinformatics, transcriptomics and proteomics technologies over the past few years have led to the discovery of numerous new peptides encoded by small open reading frames (smORFs) embedded in lncRNA transcripts (referred as microproteins here). Moreover, accumulated evidence indicates that these microproteins are involved in diverse regulatory roles in many vital processes, such as Ca2+ homeostasis, metabolism, development, stress signaling and DNA repair. However, although the limited numbers of microproteins have been functionally characterized and numerous cancer-related lncRNAs and its encoded functional microproteins were found to be able to influence tumorigenesis, the mechanisms that underlie their roles remain uncharacterized.
In a recent study published in Journal of Extracellular Vesicles, Prof. YANG Fuquan's group and Prof. CHEN Runsheng's group from the Institute of Biophysics, Chinese Academy of Sciences, and Prof. ZHANG Hongwei from Sanbo Brain Hospital, employed multiple technologies-including an improved microprotein analytical workflow and stringent criteria-to provide the first experimental evidence of abundant microproteins in cellular and circulating EVs, suggesting EV-mediated transfer of microproteins as a novel mechanism for intercellular communication. Most importantly, the preliminary data showed that the expression profile of EV microproteins in glioma patient diverged from the health donors, suggesting that the circulating microproteins in EVs might have potential diagnostic application in identifying patients with glioma.
This work was supported by the National Key R&D Program of China under Grants (2018YFA0507103 and 2018YFA0507801) and the National Natural Science Foundation of China under Grants (Grant Nos. 91640112 and 31670185).
Schematic illustration of the workflow for MS-based discovery of microproteins encoded by lncRNAs.
(Image by Fuquan Yang's group)
Article link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275822/
Contact: YANG Fuquan
Institute of Biophysics, Chinese Academy of Sciences
Beijing 100101, China
(Reported by Dr. YANG Fuquan's group)