Messenger RNAs containing premature termination codons (PTCs) are selectively eliminated by nonsense-mediated mRNA decay (NMD). Paradoxically, although cytoplasmic ribosomes are the only known species capable of PTC recognition, in mammals many PTC-containing mRNAs are apparently eliminated prior to release from the nucleus. To determine whether PTCs can influence events within the nucleus proper, we studied the immunoglobulin (Ig)-μ and T cell receptor (TCR)-β genes using fluorescent in situ hybridization (FISH). Alleles containing PTCs, but not those containing a missense mutation or a frameshift followed by frame-correcting mutations, exhibited elevated levels of pre-mRNA, which accumulated at or near the site of transcription. Our data indicate that mRNA reading frame can influence events at or near the site of gene transcription.
Mühlemann, O., Mock-Casagrande, C. S., Wang, J., Li, S., Custódio, N., Carmo-Fonseca, M., … Moore, M. J. (2001). Precursor RNAs harboring nonsense codons accumulate near the site of transcription. Molecular Cell, 8(1), 33–43. https://doi.org/10.1016/S1097-2765(01)00288-X