RFX transcription factors control a miR-150/PDAP1 axis that restrains the proliferation of human T cells

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• MicroRNAs (miRNAs) are crucial regulators within the immune system.
• Understanding miRNA targets and their transcriptional regulation is essential for deciphering immune cell function.
• The specific roles of miRNAs in T-cell activation and proliferation require further elucidation.

Purpose of the Study:

• To identify mRNA targets regulated by miRNAs in human T lymphocytes.
• To investigate the transcriptional regulation of key miRNAs, specifically miR-150.
• To uncover the regulatory mechanisms controlling T-cell proliferation.

Main Methods:

• Quantitative analysis of miRNA expression in primary human memory T helper lymphocytes.
• miRNA pull-down and sequencing to identify mRNA targets.
• CRISPR/Cas-9 genome editing to assess the function of identified targets.
• Analysis of transcription factor involvement (RFX family) in miRNA gene expression.

Main Results:

• miR-150 was the most abundant miRNA in resting T helper lymphocytes, decreasing upon activation.
• RFX transcription factors are required for constitutive MIR150 gene expression.
• PDGFA-associated protein 1 (PDAP1) was identified as a primary miR-150 target.
• PDAP1, an RNA-binding protein, significantly contributes to T-cell proliferation regulation.

Conclusions:

• A regulatory axis involving RFX factors, miR-150, and PDAP1 restrains primary human T lymphocyte proliferation.
• This study elucidates a novel mechanism controlling T-cell activation and expansion.
• Findings provide insights into the intricate molecular networks governing immune responses.