Autoimmune regulator act in synergism with thymocyte adhesion in the control of lncRNAs in medullary thymic epithelial cells

Autor(es)

Duarte, Max Jordan ^[1] ; Mascarenhas, Romario S. ^[1] ; Assis, Amanda Freire ^[1] ; Tanaka, Pedro Paranhos ^[1] ; Speck-Hernandez, Cesar A. ^[2] ; Passos, Geraldo Aleixo ^{[1, 2, 3, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Mol Immunogenet Grp, 3900 Via Bandeirantes, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Program Basic & Appl Immunol, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Basic & Oral Biol, Lab Genet & Mol Biol, Sch Dent Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Ctr Cell Based Therapy Dent, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Immunology; v. 140, p. 127-135, DEC 2021.
• Citações Web of Science: 0

Resumo

The autoimmune regulator (Aire) gene in medullary thymic epithelial cells (mTECs) encodes the AIRE protein, which interacts with its partners within the nucleus. This ``Aire complex{''} induces stalled RNA Pol II on chromatin to proceed with transcription elongation of a large set of messenger RNAs and microRNAs. Considering that RNA Pol II also transcribes long noncoding RNAs (lncRNAs), we hypothesized that Aire might be implicated in the upstream control of this RNA species. To test this, we employed a loss-of-function approach in which Aire knockout mTECs were compared to Aire wild-type mTECs for lncRNA transcriptional profiling both in vitro and in vivo model systems. RNA sequencing enables the differential expression profiling of lncRNAs when these cells adhere in vitro to thymocytes or do not adhere to them as a way to test the effect of cell adhesion. Sets of lncRNAs that are unique and that are shared in vitro and in vivo were identified. Among these, we found the Airedependent lncRNAs as for example, Platr28, Ifi30, Morrbid, Malat1, and Xist. This finding represents the first evidence that Aire mediates the transcription of lncRNAs in mTECs. Microarray hybridizations enabled us to observe that temporal thymocyte adhesion modulates the expression levels of such lncRNAs as Morrbid, Xist, and Fbxl12o after 36 h of adhesion. This finding shows the existence of a synergistic mechanism involving a link between thymocyte adhesion, Aire, and lncRNAs in mTECs that might be important for immune selfrepresentation. (AU)

• 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
• 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