Non-coding transcript in T cells (NTT): antisense transcript activates PKR and NF-kappaB in human lymphocytes.

Area of Science:

• Immunology
• Molecular Biology
• RNA Biology

Background:

• T cell activation is a complex process.
• The role of non-protein-coding RNAs (ncRNAs) in T cell activation is not fully understood.
• A specific ncRNA, the non-coding T cells transcript (NTT), is differentially expressed during human T cell activation, but its function remains unknown.

Purpose of the Study:

• To investigate the function of the 426 nt NTT transcript in human T cell activation.
• To determine the mechanism by which NTT might influence T cell activation, specifically its interaction with PKR and NF-kappaB pathways.

Main Methods:

• RT-PCR was used to detect the NTT transcript in activated human lymphocytes.
• In vitro transcription was employed to generate sense and antisense NTT transcripts.
• Sequencing confirmed the structure of the transcripts.
• PKR activation assays were performed.
• NF-kappaB activation and I-kappaBbeta degradation were assessed.

Main Results:

• A 426 nt NTT transcript was identified and characterized.
• Both sense and antisense NTT transcripts were found to be highly structured and capable of activating PKR.
• The antisense NTT transcript demonstrated significantly higher PKR activation compared to the sense transcript.
• The antisense NTT transcript more efficiently induced the degradation of I-kappaBbeta, leading to NF-kappaB activation.

Conclusions:

• NTT may play a role in lymphocyte activation through PKR-mediated NF-kappaB activation.
• The antisense NTT transcript appears to be a more potent activator of this pathway than the sense transcript.
• The precise physiological significance of the antisense NTT transcript's activity requires further investigation.