bims-micpro 2025-11-09 papers

J Mol Evol. 2025 Nov 06.

Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.

The discovery of translated alternative open reading frames (altORFs) in protein-coding regions has expanded the coding potential of viral, prokaryotic and eukaryotic genes. Experimental and computational approaches indicate that overlapping coding regions occur in mammals. In this study, I used a prediction method based on five criteria to detect novel altORFs in the human genes taken from the COSMIC Cancer Gene Census Database. Apart from the well characterized examples of human cancer-specific antigens expressed from altORF, the vast catalogue of nucleotide substitutions across cancer genes (the COSMIC database) is also likely to harbor previously uncharacterized altORFs. Under the five prediction criteria, I found 251 novel altORFs, 41 of which highly conserved in mammals and 60 uniquely resulting from nucleotide substitutions in the primary ORF of cancer genes. I found experimental evidence for 38% of the 251 novel altORFs from mass spectrometry and ribosome profiling databases. In particular, I found three altORFs in the proto-oncogene RET, three expressed altORfs in the isocitrate dehydrogenase-2 gene, and one expressed large altORF (498 nt) in the mutated TP53 gene. This study may offer clinical perspectives, because a potential source of cancer antigens may include antigens derived from translation of currently unannotated open reading frames. The altORFs detected in this study could be candidates for future experimental validation.

Keywords: COSMIC database; Evolutionary conservation; Gene expression; Mutated cancer genes; Overlapping reading frames; Prediction algorithm

DOI: https://doi.org/10.1007/s00239-025-10284-2

J Biol Chem. 2025 Nov 04. pii: S0021-9258(25)02743-7. [Epub ahead of print] 110891

Conserved +1 translational frameshifting in the S. cerevisiae gene encoding YPL034W.

Ivaylo P Ivanov, Swati Gaikwad, Byung-Sik Shin, Alan G Hinnebusch, Thomas E Dever.

Cells have developed exquisite mechanisms to ensure accurate translation of mRNA, including preventing a change in reading frame during translation elongation. A minority of chromosomally encoded genes have evolved sequences that subvert standard decoding to program +1 translational frameshifting, either constitutively or in response to external stimuli. In the yeast Saccharomyces cerevisiae, three chromosomal genes are known to employ programmed +1 translational frameshifting for expression of full-length functional products. Here, we identify a fourth yeast gene, YFS1, encompassing the existing predicted open reading frame YPL034W, with conserved programmed +1 frameshifting. Like the previously known examples, YFS1 appears to exploit peculiarities in tRNA abundance in S. cerevisiae to promote frameshifting.

Keywords: Frameshift, Recoding; Protein synthesis; RNA; Ribosome; Transfer RNA (tRNA); Translation control

DOI: https://doi.org/10.1016/j.jbc.2025.110891

Research (Wash D C). 2025 ;8 0967

Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases.

Jinghua Kong, Xinwan Su, Cefan Zhou, Weiqiang Lin, Aifu Lin, Jingfeng Tang.

Traditionally considered noncoding, various classes of noncoding RNAs (ncRNAs)-including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), primary microRNAs (pri-miRNAs), ribosomal RNAs (rRNAs), and mRNA untranslated regions (UTRs)-have recently been shown to harbor micropeptide-encoding capacity. These functionally versatile micropeptides participate in various cellular processes spanning RNA modification, transcription regulation, splicing machinery, protein translation, and posttranslational modifications. This review systematically examines 3 aspects of ncRNA-derived micropeptides: their genomic origins and biogenesis, mechanistic roles in cellular physiology, and implications in human pathologies including oncogenesis, cardiovascular disorders, and neurodegenerative conditions. We highlight emerging potential as novel therapeutic targets and diagnostic biomarkers. Furthermore, we also discuss current methodologies for micropeptide and functional characterization. In summary, the systematic identification and annotation of disease-related ncRNA-encoded micropeptides has opened up a new milestone in the field for the development of novel targeted therapies and personalized disease treatment strategies.

DOI: https://doi.org/10.34133/research.0967