Transcriptional silencing of nonsense codon-containing immunoglobulin minigenes.
Cells possess mechanisms to prevent synthesis of potentially deleterious truncated proteins caused by premature translation-termination codons (PTCs). Here, we show that PTCs can induce silencing of transcription of its cognate gene. We demonstrate for immunoglobulin (Ig)-mu minigenes expressed in HeLa cells that this transcriptional silencing is PTC specific and reversible by treatment of the cells with histone deacetylase inhibitors. Furthermore, PTC-containing Ig-mu minigenes are significantly more associated with K9-methylated histone H3 and less associated with acetylated H3 than the PTC-free Ig-mu minigene. This nonsense-mediated transcriptional gene silencing (NMTGS) is also observed with an Ig-gamma minigene, but not with several classic NMD reporter genes, suggesting that NMTGS might be specific for Ig genes. NMTGS represents a nonsense surveillance mechanism by which truncation of a gene's open reading frame (ORF) induces transcriptional silencing through chromatin remodeling. Remarkably, NMTGS is inhibited by overexpression of the putative siRNase 3'hExo, suggesting that siRNA-like molecules are involved in NMTGS.
Bühler
Marc
M
Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH-3012 Bern, Switzerland.
Mohn
Fabio
F
Stalder
Lukas
L
Mühlemann
Oliver
O
D001483:Base Sequence; D018389:Codon, Nonsense; D005092:Exonucleases / Q000378:metabolism; D020868:Gene Silencing; D005803:Genes, Immunoglobulin; D017930:Genes, Reporter; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D034622:RNA Interference; D016415:Sequence Alignment; D014158:Transcription, Genetic
D018389:Codon, Nonsense; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D007136:Immunoglobulins; D005092:Exonucleases; D006655:Histone Deacetylases; D008239:Lysine