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Aire Gene Influences the Length of the 3' UTR of mRNAs in Medullary Thymic Epithelial Cells.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 May 28; Vol. 11, pp. 1039. Date of Electronic Publication: 2020 May 28 (Print Publication: 2020). - Publication Year :
- 2020
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Abstract
- 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 the in silico analysis were statistically significant and the predicted miRNA-mRNA interactions were thermodynamically stable. Even with no in vivo or in vitro experiments, 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.<br /> (Copyright © 2020 Oliveira, Assis, Speck-Hernandez, Duarte and Passos.)
- Subjects :
- Algorithms
Animals
Antigens genetics
Binding Sites genetics
Computer Simulation
Epithelial Cells immunology
Epithelial Cells metabolism
Gene Expression Regulation
Mice
Mice, Knockout
MicroRNAs genetics
Polyadenylation genetics
Polyendocrinopathies, Autoimmune genetics
RNA-Seq
Sequence Alignment
Thymus Gland cytology
Thymus Gland immunology
Transcription Factors deficiency
AIRE Protein
3' Untranslated Regions
RNA, Messenger genetics
Thymus Gland metabolism
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32547551
- Full Text :
- https://doi.org/10.3389/fimmu.2020.01039