Microprotein-encoding RNA regulation in cells treated with pro-inflammatory and pro-fibrotic stimuli

• Published in: BMC genomics Vol. 25; no. 1; pp. 1034 - 21
• Main Authors: Pai, Victor J., Lau, Calvin J., Garcia-Ruiz, Almudena, Donaldson, Cynthia, Vaughan, Joan M., Miller, Brendan, De Souza, Eduardo V., Pinto, Antonio M., Diedrich, Jolene, Gavva, Narender R., Yu, Shan, DeBoever, Christopher, Horman, Shane R., Saghatelian, Alan
• Format: Journal Article
• Language: English
• Published: London BioMed Central 05.11.2024; BioMed Central Ltd; Springer Nature B.V; BMC
• Subjects: Algorithms; Analysis; Animal Genetics and Genomics; Animals; Biomedical and Life Sciences; Care and treatment; Cell cycle; Cell Line; Cell lines; Colon; Conserved sequence; Datasets; Diagnosis; Evolutionary conservation; Fibrosis; Gene expression; Gene Expression Regulation; Gene regulation; Genes; Genetic aspects; Genomes; Human performance; Humans; Immunomodulation; Inflammation; Inflammation - genetics; Intestine; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Life Sciences; Mice; Microarrays; Microbial Genetics and Genomics; Microproteins; Nucleotide sequence; Open reading frames; Open Reading Frames - genetics; Peptides; Peripheral blood mononuclear cells; Plant Genetics and Genomics; Proteins; Proteomes; Proteomics; Ribonucleic acid; Ribosome profiling; Ribosomes - metabolism; RNA; Small open reading frames (smORFs); Transcriptomes; United States; Small open reading frames (smORFs); Microproteins; Inflammation; Ribosome profiling; Fibrosis
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-024-10948-1

Background Recent analysis of the human proteome via proteogenomics and ribosome profiling of the transcriptome revealed the existence of thousands of previously unannotated microprotein-coding small open reading frames (smORFs). Most functional microproteins were chosen for characterization because of their evolutionary conservation. However, one example of a non-conserved immunomodulatory microprotein in mice suggests that strict sequence conservation misses some intriguing microproteins. Results We examine the ability of gene regulation to identify human microproteins with potential roles in inflammation or fibrosis of the intestine. To do this, we collected ribosome profiling data of intestinal cell lines and peripheral blood mononuclear cells and used gene expression of microprotein-encoding transcripts to identify strongly regulated microproteins, including several examples of microproteins that are only conserved with primates. Conclusion This approach reveals a number of new microproteins worthy of additional functional characterization and provides a dataset that can be queried in different ways to find additional gut microproteins of interest.