Precursor RNAs harboring nonsense codons accumulate near the site of transcription.
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)-mu and T cell receptor (TCR)-beta 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
O
Howard Hughes Medical Institute, W.M. Keck Center for Cellular Visualization, Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA.
Mock-Casagrande
C S
CS
Wang
J
J
Li
S
S
Custódio
N
N
Carmo-Fonseca
M
M
Wilkinson
M F
MF
Moore
M J
MJ
D000818:Animals; D001402:B-Lymphocytes; D015152:Blotting, Northern; D018389:Codon, Nonsense / Q000235:genetics / Q000378:metabolism*; D005803:Genes, Immunoglobulin; D019672:Genes, T-Cell Receptor / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics* / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008969:Molecular Sequence Data; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D018389:Codon, Nonsense; D007148:Immunoglobulin mu-Chains; D012322:RNA Precursors