Long RNA Sequencing and Ribosome Profiling of Inflamed ß-Cells Reveal an Extensive Translatome Landscape.
Diabetes
; 70(10): 2299-2312, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34554924
ABSTRACT
Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of the insulin-producing pancreatic ß-cells. Increasing evidence suggest that the ß-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 ß-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 ß-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 ß-cell translatome and may reveal new functional biomarkers for ß-cell distress, disease prediction and progression, and therapeutic intervention in T1D.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
/
Células Secretoras de Insulina
/
RNA Longo não Codificante
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Inflamação
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Holanda
País de publicação:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA