Transcriptional silencing of nonsense codon-containing immunoglobulin micro genes requires translation of its mRNA

Stalder, Lukas; Mühlemann, Oliver (2007). Transcriptional silencing of nonsense codon-containing immunoglobulin micro genes requires translation of its mRNA. Journal of biological chemistry, 282(22), pp. 16079-16085. Bethesda, Md.: American Society for Biochemistry and Molecular Biology 10.1074/jbc.M610595200

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Eukaryotes have evolved quality control mechanisms that prevent the expression of genes in which the protein coding potential is crippled by the presence of a premature translation-termination codon (PTC). In addition to nonsense-mediated mRNA decay (NMD), a well documented posttranscriptional consequence of the presence of a PTC in an mRNA, we recently reported the transcriptional silencing of PTC-containing immunoglobulin (Ig) mu and gamma minigenes when they are stably integrated into the genome of HeLa cells. Here we demonstrate that this transcriptional silencing of PTC-containing Ig-mu constructs requires active translation of the cognate mRNA, as it is not observed under conditions where translation of the PTC-containing mRNA is inhibited through an iron-responsive element in the 5'-untranslated region. Furthermore, RNA interference-mediated depletion of the essential NMD factor Upf1 not only abolishes NMD but also reduces the extent of nonsense-mediated transcriptional gene silencing (NMTGS). Collectively, our data indicate that NMTGS and NMD are linked, relying on the same mechanism for PTC recognition, and that the NMTGS pathway branches from the NMD pathway at a step after Upf1 function.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Mühlemann, Oliver

ISSN:

0021-9258

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:57

Last Modified:

06 Dec 2013 13:49

Publisher DOI:

10.1074/jbc.M610595200

PubMed ID:

16079-85

Web of Science ID:

000246794300016

URI:

https://boris.unibe.ch/id/eprint/24685 (FactScience: 52817)

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