Format

Send to

Choose Destination
Mol Immunol. 2019 Jul;111:209-219. doi: 10.1016/j.molimm.2019.04.006. Epub 2019 May 13.

The mouse intron-nested gene, Israa, is expressed in the lymphoid organs and involved in T-cell activation and signaling.

Author information

1
Department of Life Sciences, Health Biotechnology Program, College of Graduates Studies, Arabian Gulf University, Manama, Bahrain.
2
University of Michigan Medical School, MI, USA.
3
Department of Molecular Medicine, Princess Al-Jawhara Center for Genetics and Inherited Diseases, College of Medicine and Medical Sciences, Arabian Gulf University, Bahrain.
4
Department of Life Sciences, Health Biotechnology Program, College of Graduates Studies, Arabian Gulf University, Manama, Bahrain. Electronic address: d.fathallah@agu.edu.bh.

Abstract

We have previously reported Israa, immune-system-released activating agent, as a novel gene nested in intron 8 of the mouse Zmiz1 gene. We have also shown that Israa encodes for a novel FYN-binding protein and might be involved in the regulation of T-cell activation. In this report, we demonstrate that Israa gene product regulates the expression of a pool of genes involved in T-cell activation and signaling. Real time PCR and GFP knock-in expression analysis showed that Israa is transcribed and expressed in the spleen mainly by CD3+CD8+ cells as well as in the thymus by CD3+ (DP and DN), CD4+SP and CD8+SP cells at different developmental stages. We also showed that Israa is downregulated in T-cells following activation of T-cell receptor. Using yeast two-hybrid analysis, we identified ELF1, a transcription factor involved in T-cell regulation, as an ISRAA-binding partner. Transcriptomic analysis of an EL4 cell line overexpressing ISRAA revealed differential expression of several genes involved in T-cell signaling, activation and development. Among these genes, Prkcb, Mib2, Fos, Ndfip2, Cxxc5, B2m, Gata3 and Cd247 were upregulated whereas Itk, Socs3, Tigit, Ifng, Il2ra and FoxJ1 were downregulated. Our findings support the existence in mouse of a novel FYN-related T-cell regulation pathway involving the product of an intron-nested gene.

KEYWORDS:

Elf1; Fyn; Gene expression; Nested gene; T-cell activation; Yeast two-hybrid

PMID:
31096062
DOI:
10.1016/j.molimm.2019.04.006
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center