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| Elena Conti - | |
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Transport of mRNAs from the nucleus to the cytosol of eukaryotic cells is
linked to several quality control mechanisms that make sure that only
correctly transcribed and processed mRNAs are exported and translated. A
ubiquitous quality control mechanism is nonsense-mediated mRNA decay (NMD).
NMD is a surveillance pathway that detects mRNAs containing premature
translation termination codons (PTCs) and degrades them before they give
rise to truncated and potentially harmful protein products. NMD is present
in all eukaryotes tested and is essential for vertebrates.
In humans, detection and degradation of PTC-containing mRNAs is dependent
on translation and on splicing. The splicing-dependence is correlated to
the exon junction complex (EJC), a multiprotein assembly that is deposited
on mRNAs at the end of splicing upstream of exon junctions. EJC core
components remain bound onto mRNAs after nuclear export and influence the
cytosolic fate of mRNAs. EJC components mark aberrant mRNAs for detection
by the NMD machinery, which includes 7 essential proteins known as SMGs.
We have determined crystal structures of EJC and SMG components that give
insights into the molecular mechanisms of NMD.
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