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Thomaidou S, Slieker RC, van der Slik AR, et al. Long RNA Sequencing and Ribosome Profiling of Inflamed β-Cells Reveal an Extensive Translatome Landscape. Diabetes. 2021;70(10):2299-2312doi: 10.2337/db20-1122.
Thomaidou, S., Slieker, R. C., van der Slik, A. R., Boom, J., Mulder, F., Munoz-Garcia, A., 't Hart, L. M., Koeleman, B., Carlotti, F., Hoeben, R. C., Roep, B. O., Mei, H., & Zaldumbide, A. (2021). Long RNA Sequencing and Ribosome Profiling of Inflamed β-Cells Reveal an Extensive Translatome Landscape. Diabetes, 70(10), 2299-2312. https://doi.org/10.2337/db20-1122
Thomaidou, Sofia, et al. "Long RNA Sequencing and Ribosome Profiling of Inflamed β-Cells Reveal an Extensive Translatome Landscape." Diabetes vol. 70,10 (2021): 2299-2312. doi: https://doi.org/10.2337/db20-1122
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, Zaldumbide A. Long RNA Sequencing and Ribosome Profiling of Inflamed β-Cells Reveal an Extensive Translatome Landscape. Diabetes. 2021 Oct;70(10):2299-2312. doi: 10.2337/db20-1122. Epub 2021 Jun 15. PMID: 34554924.
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Diabetes. 2021 Oct;70(10):2299-2312. doi: 10.2337/db20-1122. Epub 2021 Jun 15.

Long RNA Sequencing and Ribosome Profiling of Inflamed β-Cells Reveal an Extensive Translatome Landscape.

Diabetes

Sofia Thomaidou, Roderick C Slieker, Arno R van der Slik, Jasper Boom, Flip Mulder, Amadeo Munoz-Garcia, Leen M 't Hart, Bobby Koeleman, Françoise Carlotti, Rob C Hoeben, Bart O Roep, Hailiang Mei, Arnaud Zaldumbide

Affiliations

  1. Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
  2. Department of Epidemiology and Biostatistics, Amsterdam Public Health Institute, Amsterdam UMC, location VUMC, Amsterdam, the Netherlands.
  3. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
  4. Sequencing Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
  5. Center for Molecular Medicine, Utrecht Medical Center, Utrecht, the Netherlands.
  6. Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
  7. Department of Diabetes Immunology, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA.
  8. Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands [email protected].

PMID: 34554924 DOI: 10.2337/db20-1122

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.

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