Exon junction complex
An exon junction complex (EJC) is a
Protein components
The EJC is made up of several key protein components:
Structure
The crystallization of the exon junction complex has revealed the structural organization of its protein components. The core of the complex is elongated with an overall dimension of 99Å by 67Å by 54Å.[21] It is organized around the eIF4AIII factor. The factor itself consists of two different types of conformations around the mRNA: closed and open. In a closed state, the two domains of eIF4AIII form composite binding sites for the 5'-adenylyl-β,γ-imidodiphosphate (ADPNP) and mRNA.[21] In the open conformation, the two domains are rotated by 160 degrees relative to closed state18. The protein components Magoh and Y14 bind together to form a heterodimer located at the 5’ pole of the EJC.[22][23][24] Magoh binds to an eIF4AIII domain through interactions between residues from its two C-terminal helices and one end of a large β-sheet.[21] Conserved residues in the linker between the two eIF4AIII domains form salt bridges or hydrogen bonds with specific residues in Magoh.[21] Other bonding occurs between the second loop of the Magoh β–sheet and the two eIF4AIII domains and their linker.[21] There is only a single partial bond formed between Y14 and eIF4AIII. This consists of a salt bridge between the conserved residues Y14 Arg108 and eIF4AIII Asp401.[21] If mutations were to occur to both of these residues, association of Magoh-Y14 with EJC would be non-existent.[25]
Mechanism
During the second step of splicing in eukaryotic cells, the EJC is deposited approximately 20-24
Recognition of a premature termination codon occurs during translation in the cytoplasm. The image shown below implies that this event is nuclear, contrary to the general view in this field. Readers should be aware that translation in the nucleus is a highly controversial subject that is not well-supported by data.[citation needed]
In nonsense mediated decay
Exon junction complexes play a major role in
EJCs are also known to take part in NMD in another way; the recruitment of the surveillance factors UPF1, UPF2 and UPF3.[32] These proteins are the most important components of the NMD mechanism. The EJC protein MAGOH, Y14 and eIF4AIII provide a binding for UPF3, which acts as a bridge between UPF2 and UPF1 forming a trimeric complex.[33] Within this complex, UPF2 and UPF3 act cooperatively to promote
Notes and references
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- ^ S2CID 6268216.