Forms a heterodimer with Magoh, but has various functions separate
from the entire EJC complex. Interestingly, the heterodimer
remains on the mRNA into the cytoplasm and requires translation in
order to be removed.
A post-splicing processing factor that aids in cytoplasmic mRNA
localization. The Magoh-Y14 heterodimer stabilizes the EJC when
bound to ssRNA.
increases translation of mRNAs with the EJC, and silencing
decreases translation. Barentsz also associates with ribosomal
subunits and translation-initiating factors. Thus, it links the
EJC to translation regulation and machinery.
III. Nuclear Export and Regulation
Pre-mRNA bound by a spliceosome is usually not exported from the
nucleus, so as to make sure that only fully-processed mRNA travels
to the cytoplasm to be translated. A protein called the mRNP
exporter binds to the EJC, both through RNA interactions and
interactions with the EJC-associated protein REF (RNA export factor)
to help pre-mRNA exit the nuclear pore complex. Interestingly, the
efficiency of unspliced mRNA export is dependent on the length;
longer mRNAs are exported more efficiently than shorter mRNAs. In
spliced mRNAs, however, once the 5' exon is long enough to bind the
EJC, the length of the spliced mRNA does not affect the export
The splicing factor, Complex with Cef1 (CWC22), binds to the eIF4AIII (to W263, D266,
D270, and D273) in such a way that the ATPase activity of
eIF4AIII is diminished and thus causes the EJC to be in an inactive
This interaction between eIF4AIII and CWC22 blocks the binding of
the Magoh-Y14 heterodimer, which is necessary for the EJC to
function. Thus, when CWC22 binds to eIF4AIII, Magoh-Y14 cannot, and
the EJC is in an inactive state. In this way CWC22
negatively regulates the EJC.
Click Here for CWC22 and eIF4AII interaction.
There are a certain number of EJCs in a cell, and they must
be recycled in order to continue tagging mature mRNAs. Once in the
cytoplasm, the ribosome-associated regulator protein (PYM) acts as
a dissociation factor. PYM binds the Magoh-Y14 heterodimer and breaks up the
EJC. Thus, the EJC can be recycled to make sure that new mRNAs can
be bound. This interaction also enhances translation of mRNAs with
bound EJCs by recruiting them directly to the ribosomal 48A
IV. Nonsense-Mediated Decay
Correctly-spliced mRNAs contain a stop codon in the final exon
of the exon-junction, but incorrectly-spliced mRNAs contain
premature termination codons (PTCs) located before (3') this proper
exon location. Unless degraded via nonsense-mediated decay
(NMD), these incorrectly-spliced mRNAs contain altered reading
frames that lead to abnormal protein production.
Click Here for mRNA decay diagram.
Nonsense-mediated decay involves mRNA with a tightly bound EJC in
the cytoplasm. The EJC is bound to hnRNPs UPF2
and UPF3 when attached to the mRNA.
Triggering of nonsense-mediated decay is caused by the trans
phosphorylation of UPF1 by SMG-1. SMG-1 is part of the SURF complex
(composed of UFP1, SMG1, SMG8, and SMG9) that recognizes the PTCs.
SMG1 then binds to the EJC through the C-terminal domain of UPF3 to
create the DECID complex that is the bridge between the SURF and
This triggers the recognition of premature termination
codons and thus nonsense-mediated decay.
This interaction of the SURF and EJC also causes the defective mRNA to
interact with P-body deadenylases, leading to the de-capping of the
poly(A) tail and the subsequent decay of the defective mRNA.
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