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Cap binding complex

From Wikipedia, the free encyclopedia

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

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

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Transcription

Steps of the translation process: Initiation : The small ribosomal subunit binds to the initiator tRNA carrying the initiator amino acid methionine. This complex then attaches to the cap structure at the 5’ end of an mRNA and scans for the start codon AUG. The process is mediated by several initiation factors. At the start codon, the large ribosomal subunit joins the complex and all initiation factors are released. The ribosome has three sites: the A-site is the entry site for new tRNA charged with amino-acid or aminoacyl-tRNA; the P-site is occupied by peptidyl-tRNA - the tRNA that carries the growing polypeptide chain; the E-site is the exit site for the tRNA after it’s done delivering the amino acid. The initiator tRNA is positioned in the P-site. Elongation: A new tRNA carrying an amino acid enters the A-site of the ribosome. On the ribosome, the anticodon of the incoming tRNA is matched against the mRNA codon positioned in the A-site. During this proof-reading, tRNA with incorrect anticodons are rejected and replaced by new tRNA that are again checked. When the right aminoacyl-tRNA enters the A-site, a peptide bond is made between the two now-adjacent amino-acids. As the peptide bond is formed, the tRNA in the P-site releases the amino-acids onto the tRNA in the A-site and becomes empty. At the same time, the ribosome moves one triplet forward on the mRNA. As a result, the empty tRNA is now in the E-site and the peptidyl tRNA is in the P-site. The A-site is now unoccupied and is ready to accept a new tRNA. The cycle is repeated for each codon on the mRNA. Termination: Termination happens when one of the three stop codons is positioned in the A-site. No tRNA can fit in the A-site at that point as there are no tRNA that match the sequence. Instead, these codons are recognized by a protein, a release factor. Binding of the release factor catalyzes the cleavage of the bond between the polypeptide and the tRNA. The polypeptide is released from the ribosome. The ribosome is disassociated into subunits and is ready for a new round of translation.

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

External links

This page was last edited on 4 January 2023, at 06:29
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