Sandbox Reserved 1654

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CPEB protein regulates the length of the polyA tail which allows to control the translation. It binds to mRNA and in association with some factors, can act as a translational repressor or activator, depending on the factors.
CPEB protein regulates the length of the polyA tail which allows to control the translation. It binds to mRNA and in association with some factors, can act as a translational repressor or activator, depending on the factors.
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A specific arrangement of CPEs in mRNA can lead to the repression of the translation. In this case, the CPEB can form a dimer which could avoid the bound of the polyA polymerase complex in 2 different ways. It could prevent the association of ePAB with the polyA tail because CPEB recruits the deadenylase PARN which reduce the length of the polyA tail. It could disrupt the interaction between the binding factors of the translation eIF4E and [https://en.wikipedia.org/wiki/EIF4G eIF4G] too, because CPEB recruits the protein Maskin which blocks eIF4G recruitment too. This prevents the bound of the cap machinery to the mRNA and therefore inhibits the translation.
+
A specific arrangement of CPEs in mRNA can lead to the repression of the translation. In this case, the CPEB can form a dimer which could avoid the bound of the polyA polymerase complex in 2 different ways. It could prevent the association of ePAB with the polyA tail because CPEB recruits the deadenylase PARN which reduce the length of the polyA tail. It could disrupt the interaction between the binding factors of the translation [https://en.wikipedia.org/wiki/EIF4E eIF4E] and [https://en.wikipedia.org/wiki/EIF4G eIF4G] too, because CPEB recruits the protein Maskin which blocks eIF4G recruitment too. This prevents the bound of the cap machinery to the mRNA and therefore inhibits the translation.
On the other hand, the CPEB can activate the translation. Indeed, in the cytoplasm, there are some repressed or silenced mRNA with a short polyA tail. They can be activated by cytoplasmic polyadenylation thanks to a hormonal stimulation. This stimulation can lead to the phosphorylation of CPEB which increase its affinity with the CPSF (Cleavage and Polyadenylation Specificity Factor) and decrease the binding between CPEB and PARN. CPSF binds to the mRNA at the sequence 3’ of the tail of the mRNA (AAUAAA) and recruits the poly(A) polymerase which leads to the elongation of the polyA tail and therefore to the activation of the translation.
On the other hand, the CPEB can activate the translation. Indeed, in the cytoplasm, there are some repressed or silenced mRNA with a short polyA tail. They can be activated by cytoplasmic polyadenylation thanks to a hormonal stimulation. This stimulation can lead to the phosphorylation of CPEB which increase its affinity with the CPSF (Cleavage and Polyadenylation Specificity Factor) and decrease the binding between CPEB and PARN. CPSF binds to the mRNA at the sequence 3’ of the tail of the mRNA (AAUAAA) and recruits the poly(A) polymerase which leads to the elongation of the polyA tail and therefore to the activation of the translation.

Revision as of 18:26, 9 January 2021

This Sandbox is Reserved from 26/11/2020, through 26/11/2021 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1643 through Sandbox Reserved 1664.
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Contents

Cytoplasmic Polyadenylation Element-Binding Protein (CPEB)

CPEB (Cytoplasmic polyadenylation element binding protein) is present in most vertebrates and invertebrates and can activate or inhibit translation. In human body, there are 4 different isoforms of CPEB (CPEB1, CPEB2, CPEB3, CPEB4), which interact differently with mRNA.

Structure

All CPEB proteins have a similar structure :

  • A N-terminal region which is a regulatory region with phosphorylation and dephosphorylation sites. This region is variable in length and composition.
  • A C-terminal region, composed of 2 recognition patterns : RRMs domains and zinc finger domains.
    • Zinc finger patterns [1]

Caption for this structure

Drag the structure with the mouse to rotate

About 54 residues with 6 cysteines and 2 histidines involved in a bond with a zinc atom, conserved for all isoforms and species. The modification of one of the eight zinc ligands destabilize the connection to the mRNA. includes :

      • A (Rd turn, residues 515-520), which is stabilized by hydrogen bonds between amide and sulfure.
      • β-hairpin with (residues 525-527) and (residues 533-535) between which there is an helical turn stabilized by hydrogen bonds.
      • An (residues 538-545) which forms the second bridge between the two zinc-binding sites. The surface-exposed face of the helix has a potential for specific intermolecular interactions with nucleic acids or proteins.
      • A 310 (residues 550-552).
      • 2 zinc binding sites, the first one is composed of and the second is composed of .
    • RRMs patterns [2]

Your Heading Here (maybe something like 'Structure')

RNA binding to RRM

Drag the structure with the mouse to rotate

Function

CPEB protein regulates the length of the polyA tail which allows to control the translation. It binds to mRNA and in association with some factors, can act as a translational repressor or activator, depending on the factors.

A specific arrangement of CPEs in mRNA can lead to the repression of the translation. In this case, the CPEB can form a dimer which could avoid the bound of the polyA polymerase complex in 2 different ways. It could prevent the association of ePAB with the polyA tail because CPEB recruits the deadenylase PARN which reduce the length of the polyA tail. It could disrupt the interaction between the binding factors of the translation eIF4E and eIF4G too, because CPEB recruits the protein Maskin which blocks eIF4G recruitment too. This prevents the bound of the cap machinery to the mRNA and therefore inhibits the translation.

On the other hand, the CPEB can activate the translation. Indeed, in the cytoplasm, there are some repressed or silenced mRNA with a short polyA tail. They can be activated by cytoplasmic polyadenylation thanks to a hormonal stimulation. This stimulation can lead to the phosphorylation of CPEB which increase its affinity with the CPSF (Cleavage and Polyadenylation Specificity Factor) and decrease the binding between CPEB and PARN. CPSF binds to the mRNA at the sequence 3’ of the tail of the mRNA (AAUAAA) and recruits the poly(A) polymerase which leads to the elongation of the polyA tail and therefore to the activation of the translation.


Disease

References

  1. ↑ Merkel DJ, Wells SB, Hilburn BC, Elazzouzi F, Perez-Alvarado GC, Lee BM. The C-Terminal Region of Cytoplasmic Polyadenylation Element Binding Protein Is a ZZ Domain with Potential for Protein-Protein Interactions. J Mol Biol. 2013 Mar 13. pii: S0022-2836(13)00156-3. doi:, 10.1016/j.jmb.2013.03.009. PMID:23500490 doi:10.1016/j.jmb.2013.03.009
  2. ↑ Afroz T, Skrisovska L, Belloc E, Guillen-Boixet J, Mendez R, Allain FH. A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins. Genes Dev. 2014 Jul 1;28(13):1498-514. doi: 10.1101/gad.241133.114. PMID:24990967 doi:http://dx.doi.org/10.1101/gad.241133.114
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