bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2022‒08‒28
three papers selected by
Thomas Farid Martínez
University of California, Irvine

  1. Crit Rev Eukaryot Gene Expr. 2022 ;32(8): 43-53
      Recently, accumulating study shows that some long non-coding RNAs (lncRNAs) have potential protein/peptide-coding capacities. In this study, the coding potential of lncRNA distal-less homeobox 6 antisense 1 (DLX6-AS1) was examined and the roles and downstream pathways of a DLX6-AS1-encoded peptide in non-small-cell lung cancer (NSCLC) cell development were investigated. The peptide-coding potential of lncRNA DLX6-AS1 was extrapolated based on prior ribosome footprint and ribosome sequencing data, IPX0002962000 mass spectrometry dataset, and Getorf bioinformatics analysis. The peptide-coding abilities of several DLX6-AS1 open reading frame (ORF) fragments, as well as protein levels were detected by Western blot assay. Cell proliferative, migratory, and invasive abilities were tested by CCK-8 or Transwell assays, respectively. Potential key biological processes and pathways related to DLX6-AS1 expression were identified by single-gene gene set enrichment analysis (GSEA) based on RNA-seq data of 510 lung adenocarcinoma samples in the TCGA GDC database. The results showed that an ORF of lncRNA DLX6-AS1 could encode a short peptide. The exogenous overexpression of this ORF-encoded peptide promoted NSCLC cell proliferation, migration, and invasion. GSEA analysis suggested that DLX6-AS1 might play crucial roles in cancer progression and wnt signaling pathway. Further analysis revealed that the exogenous overexpression of a DLX6-AS1-encoded peptide could exert its functions by activating the wnt/β-catenin pathway in NSCLC cells. In conclusion, the exogenous overexpression of a DLX6-AS1-encoded peptide could facilitate NSCLC cell growth by activating wnt/β-catenin pathway.
  2. Front Microbiol. 2022 ;13 976550
      A recent addition to the -omics toolkit, ribosome profiling, enables researchers to gain insight into the process and regulation of translation by mapping fragments of mRNA protected from nuclease digestion by ribosome binding. In this review, we discuss how ribosome profiling applied to mycobacteria has led to discoveries about translational regulation. Using case studies, we show that the traditional view of "canonical" translation mechanisms needs expanding to encompass features of mycobacterial translation that are more widespread than previously recognized. We also discuss the limitations of the method and potential future developments that could yield further insight into the fundamental biology of this important human pathogen.
    Keywords:  Mycobacterium tuberculosis; non-canonical translation; omics; ribosome profiling; translation initiation
  3. Int J Mol Sci. 2022 Aug 11. pii: 8933. [Epub ahead of print]23(16):
      There is substantial interest in mining neoantigens for cancer applications. Non-canonical proteins resulting from frameshift mutations have been identified as neoantigens in cancer. We investigated the landscape of non-canonical proteins in non-small cell lung cancer (NSCLC) and their induced immune response in the form of autoantibodies. A database of cryptoproteins was computationally constructed and comprised all alternate open reading frames (altORFs) and ORFs identified in pseudogenes, noncoding RNAs, and untranslated regions of mRNAs that did not align with known canonical proteins. Proteomic profiles of seventeen lung adenocarcinoma (LUAD) cell lines were searched to evaluate the occurrence of cryptoproteins. To assess the immunogenicity, immunoglobulin (Ig)-bound cryptoproteins in plasmas were profiled by mass spectrometry. The specimen set consisted of plasmas from 30 newly diagnosed NSCLC cases, pre-diagnostic plasmas from 51 NSCLC cases, and 102 control plasmas. An analysis of LUAD cell lines identified 420 cryptoproteins. Plasma Ig-bound analyses revealed 90 cryptoproteins uniquely found in cases and 14 cryptoproteins that had a fold-change >2 compared to controls. In pre-diagnostic samples, 17 Ig-bound cryptoproteins yielded an odds ratio ≥2. Eight Ig-bound cryptoproteins were elevated in both pre-diagnostic and newly diagnosed cases compared to controls. Cryptoproteins represent a class of neoantigens that induce an autoantibody response in NSCLC.
    Keywords:  NSCLC; altORFs; autoantibodies; neoantigens; noncanonical open reading frames