Cap binding complex

The 5' cap of eukaryotic messenger RNA is bound at all times by various cap-binding complexes (CBCs).

Surface model of the cap-binding complex (heavy chain pink, light chain yellow, m7G and GDP as balls), after PDB 1H2T.

Nuclear cap-binding complex

In the nucleus, freshly transcribed mRNA molecules are bound on the 5' cap by the nuclear cap-binding complex of Cbc1/Cbc2 in yeast or CBP20/CBP80 in metazoans. These aid in the export of the mRNA and protect it from decapping. They also serve as a marker for the so-called pioneer round of translation when the message is examined by nonsense mediated decay.[1]

Cytoplasmic cap-binding complex

After the first round of translation ("pioneer round"), CBC20/80 is replaced by the translation initiation factor eIF4E.[2] The eIF4F complex (eIF4E, eIF4G and eIF4A) then regulates translation in response to the state of the cell via its phosphorylation state and again protects the message from decapping.[3]

Decapping complex

When translationally repressed or marked for decay by various mechanisms the 5' cap is bound by the mRNA decapping enzyme DCP2. A host of proteins accompany it including UPF1, UPF2, UPF3A, Dcp1, Dhh1, XRN1, and others. The decapping enzyme removes the 5' cap leading to destruction of the message.[4]

References
  1. Isken, O.; Maquat, L.E. (2007), "Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function", Genes & Development, 21 (15): 1833–56, doi:10.1101/gad.1566807, PMID 17671086
  2. Maquat, Lynne E.; Tarn, Woan-Yuh; Isken, Olaf (August 2010). "The Pioneer Round of Translation: Features and Functions". Cell. 142 (3): 368–374. doi:10.1016/j.cell.2010.07.022. PMC 2950652. PMID 20691898.
  3. Gross, J.D.; Moerke, N.J.; Von Der Haar, T.; Lugovskoy, A.A.; Sachs, A.B.; McCarthy, J.E.G.; Wagner, G. (2003), "Ribosome Loading onto the mRNA Cap is Driven by Conformational Coupling between eIF4G and eIF4E", Cell, 115 (6): 739–750, doi:10.1016/S0092-8674(03)00975-9, PMID 14675538, S2CID 14728669
  4. Parker, R.; Sheth, U. (2007), "P Bodies and the Control of mRNA Translation and Degradation", Molecular Cell, 25 (5): 635–646, doi:10.1016/j.molcel.2007.02.011, PMID 17349952
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