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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Inflammation* / genetics
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Pancreatitis / genetics
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Peptide Chain Initiation, Translational / genetics
  • Protein Biosynthesis / genetics*
  • Protein Processing, Post-Translational
  • RNA, Long Noncoding / genetics*
  • Ribosomes / metabolism
  • Sequence Analysis, RNA / methods
  • Transcriptome


  • Biomarkers
  • RNA, Long Noncoding

Associated data

  • figshare/10.2337/figshare.14771181