Aire Gene Influences the Length of the 3 ' UTR of mRNAs in Medullary Thymic Epithelial Cells

Autor(es)

Oliveira, Ernna H. ; Assis, Amanda F. ; Speck-Hernandez, Cesar A. ; Duarte, Max Jordan ; Passos, Geraldo A.

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 11, p. 12-pg., 2020-05-28.

Resumo

Aire is a transcriptional controller in medullary thymic epithelial cells (mTECs) modulating a set of peripheral tissue antigens (PTAs) and non-PTA mRNAs as well as miRNAs. Even miRNAs exerting posttranscriptional control of mRNAs in mTECs, the composition of miRNA-mRNA networks may differ. Under reduction in Aire expression, networks exhibited greater miRNA diversity controlling mRNAs. Variations in the number of 3'UTR binding sites of Aire-dependent mRNAs may represent a crucial factor that influence the miRNA interaction. To test this hypothesis, we analyzed through bioinformatics the length of 3'UTRs of a large set of Aire-dependent mRNAs. The data were obtained from existing RNA-seq of mTECs of wild type or Aire-knockout (KO) mice. We used computational algorithms as FASTQC, STAR and HTSEQ for sequence alignment and counting reads, DESEQ2 for the differential expression, 3USS for the alternative 3'UTRs and TAPAS for the alternative polyadenylation sites. We identified 152 differentially expressed mRNAs between these samples comprising those that encode PTAs as well as transcription regulators. In Aire KO mTECs, most of these mRNAs featured an increase in the length of their 3'UTRs originating additional miRNA binding sites and new miRNA controllers. Results from thein silicoanalysis were statistically significant and the predicted miRNA-mRNA interactions were thermodynamically stable. Even with noin vivoorin vitroexperiments, they were adequate to show that lack of Aire in mTECs might favor the downregulation of PTA mRNAs and transcription regulators via miRNA control. This could unbalance the overall transcriptional activity in mTECs and thus the self-representation. (AU)

• Processo FAPESP: 17/10780-4 - Efeito de mutações no gene AIRE (síndrome APS1) induzidas por CRISPR-Cas9 na conformação da proteína, no transcriptoma de células mTEC e na sua interação com timócitos
• Beneficiário: Geraldo Aleixo da Silva Passos Júnior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/17481-1 - A função do gene AIRE e de micro RNAs no controle da adesão de células tímicas epiteliais medulares com timócitos
• Beneficiário: Geraldo Aleixo da Silva Passos Júnior
• Modalidade de apoio: Auxílio à Pesquisa - Regular