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Comparative analyses of vertebrate CPEB proteins define two subfamilies with coordinated yet distinct functions in post-transcriptional gene regulation.
Duran-Arqué B
,
Cañete M
,
Castellazzi CL
,
Bartomeu A
,
Ferrer-Caelles A
,
Reina O
,
Caballé A
,
Gay M
,
Arauz-Garofalo G
,
Belloc E
,
Mendez R
.
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BACKGROUND: Vertebrate CPEB proteins bind mRNAs at cytoplasmic polyadenylation elements (CPEs) in their 3' UTRs, leading to cytoplasmic changes in their poly(A) tail lengths; this can promote translational repression or activation of the mRNA. However, neither the regulation nor the mechanisms of action of the CPEB family per se have been systematically addressed to date.
RESULTS: Based on a comparative analysis of the four vertebrate CPEBs, we determine their differential regulation by phosphorylation, the composition and properties of their supramolecular assemblies, and their target mRNAs. We show that all four CPEBs are able to recruit the CCR4-NOT deadenylation complex to repress the translation. However, their regulation, mechanism of action, and target mRNAs define two subfamilies. Thus, CPEB1 forms ribonucleoprotein complexes that are remodeled upon a single phosphorylation event and are associated with mRNAs containing canonical CPEs. CPEB2-4 are regulated by multiple proline-directed phosphorylations that control their liquid-liquid phase separation. CPEB2-4 mRNA targets include CPEB1-bound transcripts, with canonical CPEs, but also a specific subset of mRNAs with non-canonical CPEs.
CONCLUSIONS: Altogether, these results show how, globally, the CPEB family of proteins is able to integrate cellular cues to generate a fine-tuned adaptive response in gene expression regulation through the coordinated actions of all four members.
Afroz,
A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins.
2014, Pubmed
Afroz,
A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins.
2014,
Pubmed
Barnard,
Symplekin and xGLD-2 are required for CPEB-mediated cytoplasmic polyadenylation.
2004,
Pubmed
,
Xenbase
Bava,
CPEB1 coordinates alternative 3'-UTR formation with translational regulation.
2013,
Pubmed
Beaudoing,
Patterns of variant polyadenylation signal usage in human genes.
2000,
Pubmed
Belloc,
A deadenylation negative feedback mechanism governs meiotic metaphase arrest.
2008,
Pubmed
,
Xenbase
Benner,
Prospects of Fine-Mapping Trait-Associated Genomic Regions by Using Summary Statistics from Genome-wide Association Studies.
2017,
Pubmed
Calderone,
Sequential Functions of CPEB1 and CPEB4 Regulate Pathologic Expression of Vascular Endothelial Growth Factor and Angiogenesis in Chronic Liver Disease.
2016,
Pubmed
Chao,
Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors.
2013,
Pubmed
Chen,
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool.
2013,
Pubmed
Chen,
CPEB2-dependent translation of long 3'-UTR Ucp1 mRNA promotes thermogenesis in brown adipose tissue.
2018,
Pubmed
de Moor,
The Mos pathway regulates cytoplasmic polyadenylation in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Drisaldi,
SUMOylation Is an Inhibitory Constraint that Regulates the Prion-like Aggregation and Activity of CPEB3.
2015,
Pubmed
Fagoonee,
The RNA binding protein ESRP1 fine-tunes the expression of pluripotency-related factors in mouse embryonic stem cells.
2013,
Pubmed
Ferrell,
Ultrasensitivity part II: multisite phosphorylation, stoichiometric inhibitors, and positive feedback.
2014,
Pubmed
Gambarotto,
Ultrastructure expansion microscopy (U-ExM).
2021,
Pubmed
Giangarrà,
Global Analysis of CPEBs Reveals Sequential and Non-Redundant Functions in Mitotic Cell Cycle.
2015,
Pubmed
Guillén-Boixet,
CPEB4 is regulated during cell cycle by ERK2/Cdk1-mediated phosphorylation and its assembly into liquid-like droplets.
2016,
Pubmed
,
Xenbase
Hake,
CPEB is a specificity factor that mediates cytoplasmic polyadenylation during Xenopus oocyte maturation.
1994,
Pubmed
,
Xenbase
Huang,
Facilitation of dendritic mRNA transport by CPEB.
2003,
Pubmed
Huang,
N-methyl-D-aspartate receptor signaling results in Aurora kinase-catalyzed CPEB phosphorylation and alpha CaMKII mRNA polyadenylation at synapses.
2002,
Pubmed
,
Xenbase
Igea,
Meiosis requires a translational positive loop where CPEB1 ensues its replacement by CPEB4.
2010,
Pubmed
,
Xenbase
Ivshina,
Cytoplasmic polyadenylation element binding proteins in development, health, and disease.
2014,
Pubmed
Kato,
Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels.
2012,
Pubmed
Kim,
RINGO/cdk1 and CPEB mediate poly(A) tail stabilization and translational regulation by ePAB.
2007,
Pubmed
,
Xenbase
Kim,
Opposing polymerase-deadenylase activities regulate cytoplasmic polyadenylation.
2006,
Pubmed
,
Xenbase
Kok,
Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA.
2007,
Pubmed
Konopacka,
RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response.
2015,
Pubmed
Koulouras,
EasyFRAP-web: a web-based tool for the analysis of fluorescence recovery after photobleaching data.
2018,
Pubmed
Kuleshov,
Enrichr: a comprehensive gene set enrichment analysis web server 2016 update.
2016,
Pubmed
Langmead,
Fast gapped-read alignment with Bowtie 2.
2012,
Pubmed
Lawrence,
Scalable Genomics with R and Bioconductor.
2014,
Pubmed
Love,
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.
2014,
Pubmed
Maillo,
Circadian- and UPR-dependent control of CPEB4 mediates a translational response to counteract hepatic steatosis under ER stress.
2017,
Pubmed
Mendez,
Phosphorylation of CPEB by Eg2 mediates the recruitment of CPSF into an active cytoplasmic polyadenylation complex.
2000,
Pubmed
,
Xenbase
Mendez,
Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA.
2000,
Pubmed
,
Xenbase
Mendez,
Differential mRNA translation and meiotic progression require Cdc2-mediated CPEB destruction.
2002,
Pubmed
,
Xenbase
Novoa,
Mitotic cell-cycle progression is regulated by CPEB1 and CPEB4-dependent translational control.
2010,
Pubmed
,
Xenbase
Pascual,
The RNA binding protein CPEB2 regulates hormone sensing in mammary gland development and luminal breast cancer.
2020,
Pubmed
Pavlopoulos,
Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and memory storage.
2011,
Pubmed
Peuchen,
Phosphorylation Dynamics Dominate the Regulated Proteome during Early Xenopus Development.
2017,
Pubmed
,
Xenbase
Phung,
The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma.
2019,
Pubmed
Piqué,
A combinatorial code for CPE-mediated translational control.
2008,
Pubmed
,
Xenbase
Planet,
htSeqTools: high-throughput sequencing quality control, processing and visualization in R.
2012,
Pubmed
Rouhana,
Vertebrate GLD2 poly(A) polymerases in the germline and the brain.
2005,
Pubmed
,
Xenbase
Roux,
A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells.
2012,
Pubmed
Setoyama,
Mechanism of degradation of CPEB during Xenopus oocyte maturation.
2007,
Pubmed
,
Xenbase
Stebbins-Boaz,
Maskin is a CPEB-associated factor that transiently interacts with elF-4E.
1999,
Pubmed
,
Xenbase
Stepien,
RNA-binding profiles of Drosophila CPEB proteins Orb and Orb2.
2016,
Pubmed
Sun,
Molecular basis for the recognition of the human AAUAAA polyadenylation signal.
2018,
Pubmed
Szklarczyk,
The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible.
2017,
Pubmed
Tay,
Germ cell differentiation and synaptonemal complex formation are disrupted in CPEB knockout mice.
2001,
Pubmed
Wang,
Comparative in silico analyses of cpeb1-4 with functional predictions.
2010,
Pubmed
Weill,
Translational control by changes in poly(A) tail length: recycling mRNAs.
2012,
Pubmed
Wühr,
Deep proteomics of the Xenopus laevis egg using an mRNA-derived reference database.
2014,
Pubmed
,
Xenbase
Yang,
Genome-wide analysis identifies cis-acting elements regulating mRNA polyadenylation and translation during vertebrate oocyte maturation.
2020,
Pubmed
,
Xenbase
Youn,
High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies.
2018,
Pubmed