Nonsense-associated altered splicing: a frame-dependent response distinct from nonsense-mediated decay.

Nonsense-associated altered splicing (NAS) is a putative correction response that upregulates alternatively spliced transcripts that have skipped offending premature termination codons (PTCs). Here, we examined whether NAS has characteristics in common with nonsense-mediated decay (NMD), a surveillance mechanism that degrades PTC-bearing mRNAs. We discovered that although NAS shared the need for a Kozak AUG to define frame, it differed from NMD.

Alternatively spliced TCR mRNA induced by disruption of reading frame.

Nonsense codons that prematurely terminate translation generate potentially deleterious truncated proteins. Here, we show that the T cell receptor-beta (TCRbeta) gene, which acquires in-frame nonsense codons at high frequency during normal lymphocyte development, gives rise to an alternatively spliced transcript [alternative messenger RNA (alt-mRNA)] that skips the offending mutations that generate such nonsense codons. This alt-mRNA is up-regulated by a transfer RNA-dependent scanning mechanism that responds specifically to mutations that disrupt the reading frame.