Precursor RNAs harboring nonsense codons accumulate near the site of transcription

Messenger RNAs containing premature termination codons (PTCs) are selective ly eliminated by nonsensemediated mRNA decay (NMD). Paradoxically, although cytoplasmic ribosomes are the only known species capable of PTC recognitio n, in mammals many PTC-containing mRNAs are apparently eliminated prior to release from the nucleus. To determine whether PTCs can influence events wi thin the nucleus proper, we studied the immunoglobulin (Ig)-mu and T cell r eceptor (TCR)-beta genes using fluorescent in situ hybridization (FISH). Al leles containing PTCs, but not those containing a missense mutation or a fr ameshift followed by frame-correcting mutations, exhibited elevated levels of pre-mRNA, which accumulated at or near the site of transcription. Our da ta indicate that mRNA reading frame can influence events at or near the sit e of gene transcription.