1. Long RNA Sequencing and Ribosome Profiling of Inflamed β-Cells Reveal an Extensive Translatome Landscape.
- Author
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Thomaidou S, Slieker RC, van der Slik AR, Boom J, Mulder F, Munoz-Garcia A, 't Hart LM, Koeleman B, Carlotti F, Hoeben RC, Roep BO, Mei H, and Zaldumbide A
- Subjects
- Autoimmunity genetics, Biomarkers analysis, Biomarkers metabolism, Cells, Cultured, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 metabolism, Diabetes Mellitus, Type 1 pathology, Gene Expression Profiling methods, Humans, Insulin-Secreting Cells pathology, Pancreatitis genetics, Pancreatitis metabolism, Pancreatitis pathology, Peptide Chain Initiation, Translational genetics, Protein Processing, Post-Translational, Ribosomes metabolism, Sequence Analysis, RNA methods, Transcriptome, Inflammation genetics, Inflammation metabolism, Inflammation pathology, Insulin-Secreting Cells metabolism, Protein Biosynthesis genetics, RNA, Long Noncoding genetics
- Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of the insulin-producing pancreatic β-cells. Increasing evidence suggest that the β-cells themselves contribute to their own destruction by generating neoantigens through the production of aberrant or modified proteins that escape central tolerance. We recently demonstrated that ribosomal infidelity amplified by stress could lead to the generation of neoantigens in human β-cells, emphasizing the participation of nonconventional translation events in autoimmunity, as occurring in cancer or virus-infected tissues. Using a transcriptome-wide profiling approach to map translation initiation start sites in human β-cells under standard and inflammatory conditions, we identify a completely new set of polypeptides derived from noncanonical start sites and translation initiation within long noncoding RNA. Our data underline the extreme diversity of the β-cell translatome and may reveal new functional biomarkers for β-cell distress, disease prediction and progression, and therapeutic intervention in T1D., (© 2021 by the American Diabetes Association.)
- Published
- 2021
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