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Alternative splicing induced by nonsense mutations in the immunoglobulin mu VDJ exon is independent of truncation of the open reading frame

Bühler, Marc and Mühlemann, Oliver. (2005) Alternative splicing induced by nonsense mutations in the immunoglobulin mu VDJ exon is independent of truncation of the open reading frame. RNA, Vol. 11, H. 2. pp. 139-146.

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Official URL: http://edoc.unibas.ch/dok/A5251095

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Abstract

In addition to triggering nonsense-mediated mRNA decay (NMD), premature translation-termination codons (PTCs) frequently induce alternative splicing, an observation referred to as nonsense-associated alternative splicing (NAS). In many cases, NAS is induced because the nonsense mutation alters a splicing signal, such as inactivating an exonic splicing enhancer. However, for a few genes, NAS was reported to be PTC specific, implying that a translation signal could influence splicing. Here, we investigated whether production of a previously undetected alternatively spliced transcript from immunoglobulin mu (Ig-mu) depends on premature termination of the open reading frame. We show that PTCs at different positions in the VDJ exon of an Ig-mu minigene activate usage of an alternative 3' splice site, generating an alternative transcript that lacks the initial PTC and a previously identified NMD-promoting element (NPE), but contains new PTCs because of a frame shift. Corroborating the importance of the NPE for maximal NMD response, the alternative transcript is only moderately down-regulated by NMD. We further demonstrate that NAS of Ig-mu minigene transcripts is not PTC specific. This finding, together with our results that contradict the previously reported frame dependence of TCR-beta NAS, challenges the idea that cells might possess mechanisms that would allow regulation of splice site selection in response to premature termination of the ORF.
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI
UniBasel Contributors:Bühler, Marc
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cambridge University Press
ISSN:1355-8382
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:19
Deposited On:22 Mar 2012 13:16

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