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EJC-independent degradation of nonsense immunoglobulin-μ mRNA depends on 3′ UTR length

Abstract

Inconsistent with prevailing models for nonsense-mediated mRNA decay (NMD) in mammals, the mRNA levels of immunoglobulin-μ (Ig-μ) genes with premature termination codons (PTCs) in the penultimate exon are still reduced by NMD when the intron furthest downstream is deleted. As in yeast, this exon junction complex-independent NMD of Ig-μ mRNAs depends on the distance between the termination codon and the poly(A) tail and suggests an evolutionarily conserved mode of PTC recognition.

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Figure 1: NMD does not require a downstream intron or the EJC factor eIF4AIII.
Figure 2: The distance between the termination codon and the poly(A) tail determines whether NMD is elicited.

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Acknowledgements

We thank J. Lykke-Andersen, J. Lingner, M.J. Moore, A. Kulozik and L.E. Maquat for antibodies and plasmids. This work was supported by the Kanton Bern and by grants to O.M. from the Swiss National Foundation, the Novartis Foundation for Biomedical Research and the Helmut Horten Foundation.

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Correspondence to Oliver Mühlemann.

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Supplementary information

Supplementary Fig. 1

The various miniμ constructs are spliced as predicted. (PDF 112 kb)

Supplementary Fig. 2

Downregulation of PTC+ miniμ C3/C4 mRNA depends on translation. (PDF 30 kb)

Supplementary Methods (PDF 84 kb)

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Bühler, M., Steiner, S., Mohn, F. et al. EJC-independent degradation of nonsense immunoglobulin-μ mRNA depends on 3′ UTR length. Nat Struct Mol Biol 13, 462–464 (2006). https://doi.org/10.1038/nsmb1081

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