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Out-of-frame T cell receptor beta transcripts are eliminated by multiple pathways in vivo

Grace K Mahowald1, Michael A Mahowald, Clara Moon

  • 1Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, United States of America.

Plos One
|July 19, 2011
PubMed

Insights

Nonsense-mediated decay (NMD) efficiently clears non-productive T cell receptor beta (Tcrb) transcripts with premature termination codons (PTCs). Optimal transcript clearance in T cells requires a downstream intron, highlighting its crucial role in gene regulation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Non-productive antigen receptor genes with frame shifts occur in mature lymphocytes.
  • Transcripts with premature termination codons (PTCs) risk encoding truncated proteins unless degraded by nonsense-mediated decay (NMD).
  • NMD pathways can be intron-dependent or independent, with other mechanisms also inactivating PTC-containing transcripts.

Purpose of the Study:

  • To investigate the in vivo mechanisms governing the clearance of premature termination codon-containing T cell receptor beta (Tcrb) transcripts in T cells.
  • To determine the role of downstream introns in the nonsense-mediated decay (NMD) of Tcrb transcripts.

Main Methods:

  • Generation and analysis of gene-targeted mice with modifications at the endogenous T cell receptor beta (Tcrb) locus.
  • In vivo studies assessing transcript clearance in T cells.

Main Results:

  • Optimal clearance of PTC-containing Tcrb transcripts in T cells is dependent on the presence of a downstream intron.
  • This finding underscores the importance of intron-mediated regulation in controlling non-productive gene expression.

Conclusions:

  • The presence of a downstream intron is essential for efficient nonsense-mediated decay (NMD) of premature termination codon-containing T cell receptor beta (Tcrb) transcripts in T cells.
  • This study elucidates a key regulatory mechanism ensuring T cell receptor fidelity and function.

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