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Long-RNA Sequencing and Ribosome Profiling of Inflamed Beta-Cells Reveal an Extensive Translatome Landscape
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posted on 2021-06-15, 22:58 authored by Sofia Thomaidou, Roderick C. Slieker, Arno R. van der Slik, Jasper Boom, Flip Mulder, Amadeo Munoz-Garcia, Leen M. ‘t Hart, Bobby Koeleman, Francoise Carlotti, Rob C. Hoeben, Bart O. Roep, Hailiang Mei, Arnaud ZaldumbideType 1 diabetes is an autoimmune disease characterized by autoreactive
T-cell mediated destruction of the insulin-producing pancreatic beta-cells.
Increasing evidence suggest that the beta-cells themselves contribute to their
own destruction by generating neo-antigens through the production of aberrant
or modified proteins that escape central tolerance. We have recently
demonstrated that ribosomal infidelity amplified by stress could lead to the
generation of neoantigens in human beta-cells, emphasizing the participation of
nonconventional translation events to autoimmunity, as occurring in cancer or
virus-infected tissues. Using a transcriptome-wide profiling approach to map
translation initiation start sites in human beta-cells under standard and
inflammatory conditions, we identify a completely new set of polypeptides
derived from non-canonical start sites and translation initiation within
lncRNA. Our data underline the extreme diversity of the beta-cell translatome
and may reveal new functional biomarkers for beta-cell distress, disease
prediction and progression and therapeutic intervention in type 1 diabetes.