Transient CPEB dimerization and translational control

Lin, Chien-Ling; Huang, Yen‐Tsung; Richter, Joel D.

doi:10.1261/rna.031682.111

Cited by 11 publications

(18 citation statements)

References 41 publications

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“…Recent evidence also demonstrates that CPEB resides in two distinct pools in oocytes: one pool is bound to RNA while the second forms a homodimer through its RNA binding regions and thus does not bind RNA. The homodimers are destroyed very rapidly upon oocyte maturation, perhaps releasing essential factors to associate with the cytoplasmic polyadenylation complex (32).…”

Section: Discussionmentioning

confidence: 99%

An Unusual Two-Step Control of CPEB Destruction by Pin1

Nechama

Lin

Richter

2013

Molecular and Cellular Biology

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Cytoplasmic polyadenylation is a conserved mechanism that controls mRNA translation and stability. A key protein that promotes polyadenylation-induced translation of mRNAs in maturing Xenopus oocytes is the cytoplasmic polyadenylation element binding protein (CPEB). During this meiotic transition, CPEB is subjected to phosphorylation-dependent ubiquitination and partial destruction, which is necessary for successive waves of polyadenylation of distinct mRNAs. Here we identify the peptidylprolyl cis-trans isomerase Pin1 as an important factor mediating CPEB destruction. Pin1 interacts with CPEB in an unusual manner in which it occurs prior to CPEB phosphorylation and prior to Pin1 activation by serine 71 dephosphorylation. Upon induction of maturation, CPEB becomes phosphorylated, which occurs simultaneously with Pin1 dephosphorylation. At this time, the CPEB-Pin1 interaction requires cdk1-catalyzed CPEB phosphorylation on S/T-P motifs. Subsequent CPEB ubiquitination and destruction are mediated by a conformational change induced by Pin1 isomerization of CPEB. Similar to M phase progression in maturing Xenopus oocytes, the destruction of CPEB during the mammalian cell cycle requires Pin1 as well. These data identify Pin1 as a new and essential factor regulating CPEB degradation.

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Section: Discussionmentioning

confidence: 99%

An Unusual Two-Step Control of CPEB Destruction by Pin1

Nechama

Lin

Richter

2013

Molecular and Cellular Biology

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“…(19) that CPEB1 dimerization via its RNA binding regions functions as a regulatory mechanism during cell cycle. We therefore consider the possibility that protein dimerization could also occur in CPEB4.…”

Section: Resultsmentioning

confidence: 99%

RNA recognition and self-association of CPEB4 is mediated by its tandem RRM domains

Schelhorn

Gordon

Ruiz

et al. 2014

Nucleic Acids Research

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Cytoplasmic polyadenylation is regulated by the interaction of the cytoplasmic polyadenylation element binding proteins (CPEB) with cytoplasmic polyadenylation element (CPE) containing mRNAs. The CPEB family comprises four paralogs, CPEB1–4, each composed of a variable N-terminal region, two RNA recognition motif (RRM) and a C-terminal ZZ-domain. We have characterized the RRM domains of CPEB4 and their binding properties using a combination of biochemical, biophysical and NMR techniques. Isothermal titration calorimetry, NMR and electrophoretic mobility shift assay experiments demonstrate that both the RRM domains are required for an optimal CPE interaction and the presence of either one or two adenosines in the two most commonly used consensus CPE motifs has little effect on the affinity of the interaction. Both the single RRM1 and the tandem RRM1–RRM2 have the ability to dimerize, although representing a minor population. Self-association does not affect the proteins’ ability to interact with RNA as demonstrated by ion mobility–mass spectrometry. Chemical shift effects measured by NMR of the apo forms of the RRM1–RRM2 samples indicate that the two domains are orientated toward each other. NMR titration experiments show that residues on the β-sheet surface on RRM1 and at the C-terminus of RRM2 are affected upon RNA binding. We propose a model of the CPEB4 RRM1–RRM2–CPE complex that illustrates the experimental data.

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“…CPEB1 is degraded during the completion of meiosis I through a mechanism involving phosporylation by a polo like kinase (PLK1) and the cyclin dependent kinase CDK1 (cdc2) and ubiquitination by the E3 ligase BTRC (SCF β‐TrCP ) . This degradation has been proposed to be predominantly on nonRNA bound CPEB1 which is sequestered in the form of a dimer . SYMPK‐bound CPEB1 levels, presumably representing RNA bound CPEB1 in polyadenylation competent complexes, remain unchanged during oogenesis …”

Section: Cytoplasmic Polyadenylation Of Mrnas In Germ Cells and Embryosmentioning

confidence: 99%

Specificity factors in cytoplasmic polyadenylation

2013

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Poly(A) tail elongation after export of an messenger RNA (mRNA) to the cytoplasm is called cytoplasmic polyadenylation. It was first discovered in oocytes and embryos, where it has roles in meiosis and development. In recent years, however, has been implicated in many other processes, including synaptic plasticity and mitosis. This review aims to introduce cytoplasmic polyadenylation with an emphasis on the factors and elements mediating this process for different mRNAs and in different animal species. We will discuss the RNA sequence elements mediating cytoplasmic polyadenylation in the 3′ untranslated regions of mRNAs, including the CPE, MBE, TCS, eCPE, and C-CPE. In addition to describing the role of general polyadenylation factors, we discuss the specific RNA binding protein families associated with cytoplasmic polyadenylation elements, including CPEB (CPEB1, CPEB2, CPEB3, and CPEB4), Pumilio (PUM2), Musashi (MSI1, MSI2), zygote arrest (ZAR2), ELAV like proteins (ELAVL1, HuR), poly(C) binding proteins (PCBP2, αCP2, hnRNP-E2), and Bicaudal C (BICC1). Some emerging themes in cytoplasmic polyadenylation will be highlighted. To facilitate understanding for those working in different organisms and fields, particularly those who are analyzing high throughput data, HUGO gene nomenclature for the human orthologs is used throughout. Where human orthologs have not been clearly identified, reference is made to protein families identified in man. © 2013 John Wiley & Sons, Ltd.

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Transient CPEB dimerization and translational control

Cited by 11 publications

References 41 publications

An Unusual Two-Step Control of CPEB Destruction by Pin1

An Unusual Two-Step Control of CPEB Destruction by Pin1

RNA recognition and self-association of CPEB4 is mediated by its tandem RRM domains

Specificity factors in cytoplasmic polyadenylation

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