Article

Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells

Department of Biochemistry and Biophysics, University of Rochester, School of Medicine and Dentistry, Rochester, New York, USA.
Current Opinion in Cell Biology (Impact Factor: 8.74). 07/2005; 17(3):309-15. DOI: 10.1016/j.ceb.2005.03.002
Source: PubMed

ABSTRACT Nonsense-mediated mRNA decay (NMD) generally involves nonsense codon recognition by translating ribosomes at a position approximately 25 nts upstream of a splicing-generated exon junction complex of proteins. As such, NMD provides a means to degrade abnormal mRNAs that encode potentially deleterious truncated proteins. Additionally, an estimated one-third of naturally occurring, alternatively spliced mRNAs is also targeted for NMD. Given the extraordinary frequency of alternative splicing together with data indicating that naturally occurring transcripts other than alternatively spliced mRNAs are likewise targeted for NMD, it is believed that mammalian cells routinely utilize NMD to achieve proper levels of gene expression.

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Available from: Fabrice Lejeune, Jul 31, 2015
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    • "Missense mutations constitute about 42% of all EFNB1 mutations and lead to the exchange of amino acid residues that are important for receptor-ligand interaction and signaling (Twigg et al., 2004; Wieland et al., 2005). Truncating mutations are associated with extremely reduced transcript levels via a mechanism known as nonsense-mediated RNA decay that prevents the translation of transcripts carrying PTCs (Lejeune and Maquat, 2005). Only a minority of EFNB1 truncating or splice-site mutations have been investigated at the expression level (Makarov et al., 2010; Wieland et al., 2008). "
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    • "S6K1, when phosphorylated, also induces translation of spliced RNAs, through recruitment to the EJC (exon-junction complex) mediated by SKAR [102]. This EJC leads quality management on mRNAs, eliminating those that have PTCs (premature termination codons) (reviewed in [113]). "
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    • "In other instances " unsuited " mRNAs are prevented from crossing the nuclear membrane, a selection structure which emerged in eukaryotes to separate intron-containing RNAs from the translation apparatus. In addition, other cellular systems may degrade irregularly spliced or mutated mRNAs (nonsensemediated decay, NMD) [4] [5] [6] or, eventually, altered proteins may be ubiquitinated and proteasome-degraded [7]. However , in some cases, despite all these control mechanisms, an irregular splicing or a disruption of the physiological alternative splicing may impair cell functions and bring about severe illnesses [8] [9] [10]. "
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