1.A.123.  The LncRNA-encoded Pentameric Peptide Channel (LPPC) Family

Glioma exhibit abnormalities in the behavior of water and ion channels which regulate tumor proliferation, migration, apoptosis, and differentiation. Some long noncoding RNAs (lncRNAs) containing small open reading frames can encode small peptides that form oligomeric channels for water and/or ion permeation. Cao et al. 2021 used bioinformatics methods to identify and evaluate lncRNAs, which encode small transmembrane peptides in gliomas. They constructed a predictive model and predicted the oligomeric channel activity of peptides by identifying the lncRNA ORFs. They found that one key human hub lncRNA, namely, DLEU1, which contains two small ORFs (ORF1 and ORF8), encodes small peptides that form pentameric channels. ORF1, of 34 aas, has the sequence:

MRRIIVVHASPFASSVAVLLLLARACSAFAKPRR

with one central TMS. The mechanics of water and ion (Na⁺ and Cl^-) transport through this pentameric channel were simulated (Cao et al. 2021). The potential mean force of the H₂O molecules along the two ORF-encoded peptide channels indicated that the energy barrier was different between ORF1 and ORF8. The ORF1-encoded peptide pentamer acted as a self-assembled water channel but not as an ion channel, and the ORF8 peptide permeated neither ions nor water. This work describes new methods and theoretical support for further elucidation of the function of lncRNA-encoded small peptides and their role in cancer.