title: Precursor RNAs harboring nonsense codons accumulate near the site of transcription.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, W.M. Keck Center for Cellular Visualization, Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA.
authors.forename: O
authors.initials: O
authors.lastname: Mühlemann
authors.forename: C S
authors.initials: CS
authors.lastname: Mock-Casagrande
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Custódio
authors.forename: M
authors.initials: M
authors.lastname: Carmo-Fonseca
authors.forename: M F
authors.initials: MF
authors.lastname: Wilkinson
authors.forename: M J
authors.initials: MJ
authors.lastname: Moore
mesh_terms: 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
chemical_list: D018389:Codon, Nonsense; D007148:Immunoglobulin mu-Chains; D012322:RNA Precursors