scholarly journals Ataxin-2, Twenty-four and Dicer-2 are components of a non-canonical cytoplasmic polyadenylation complex

2021 ◽  
Author(s):  
Hima Priyanka Nadimpalli ◽  
Tanit Guitart ◽  
Olga Coll ◽  
Fátima Gebauer
Keyword(s):  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Mrna Translation ◽  
Early Embryogenesis ◽  
High Confidence ◽  
Interference Factor ◽  
Cytoplasmic Polyadenylation ◽  
Mrna Targets ◽  
Ataxin 2

Cytoplasmic polyadenylation is a mechanism to promote mRNA translation in a wide variety of biological contexts. A canonical complex centered around the conserved RNA-binding protein family CPEB has been shown to be responsible for this process. We have previously reported evidence for an alternative non-canonical, CPEB-independent complex in Drosophila, of which the RNA-interference factor Dicer-2 is a component. Here, we investigate Dicer-2 mRNA targets and protein co-factors in cytoplasmic polyadenylation. Using RIP-Seq analysis we identify hundreds of novel Dicer-2 target transcripts, ~50% of which were previously found as targets of the cytoplasmic poly(A) polymerase Wispy, suggesting widespread roles of Dicer-2 in cytoplasmic polyadenylation. Large-scale immunoprecipitation revealed Ataxin-2 and Twenty-four among the high-confidence interactors of Dicer-2. Functional analysis indicate that both factors form an RNA-independent complex with Dicer-2, and are required for cytoplasmic polyadenylation of Dicer-2 targets. Our results reveal the composition of a novel cytoplasmic polyadenylation complex that operates during Drosophila early embryogenesis.

scholarly journals A continuous model of physiological prion aggregation suggests a role for Orb2 in gating long-term synaptic information

2018 ◽  
Vol 5 (12) ◽  
pp. 180336
Author(s):  
Michele Sanguanini ◽  
Antonino Cattaneo
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mrna Translation ◽  
Continuous Model ◽  
Cellular Level ◽  
Long Term Memory ◽  
Cytoplasmic Polyadenylation ◽  
Differential Model

The regulation of mRNA translation at the level of the synapse is believed to be fundamental in memory and learning at the cellular level. The family of cytoplasmic polyadenylation element binding (CPEB) proteins emerged as an important RNA-binding protein family during development and in adult neurons. Drosophila Orb2 (homologue of mouse CPEB3 protein and of the neural isoform of Aplysia CPEB) has been found to be involved in the translation of plasticity-dependent mRNAs and has been associated with long-term memory. Orb2 protein presents two main isoforms, Orb2A and Orb2B, which form an activity-induced amyloid-like functional aggregate, thought to be the translation-inducing state of the RNA-binding protein. Here we present a first two-states continuous differential model for Orb2A–Orb2B aggregation. This model provides new working hypotheses for studying the role of prion-like CPEB proteins in long-term synaptic plasticity. Moreover, this model can be used as a first step to integrate translation- and protein aggregation-dependent phenomena in synaptic facilitation rules.

scholarly journals The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x

2007 ◽  
Vol 176 (7) ◽  
pp. 929-939 ◽  
Author(s):  
Maria Paola Paronetto ◽  
Tilman Achsel ◽  
Autumn Massiello ◽  
Charles E. Chalfant ◽  
Claudio Sette
Keyword(s):  
Alternative Splicing ◽  
Tyrosine Phosphorylation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Live Cells ◽  
Hnrnp A1 ◽  
Splice Site Selection ◽  
Subnuclear Localization ◽  
Mrna Targets

The RNA-binding protein Sam68 is involved in apoptosis, but its cellular mRNA targets and its mechanism of action remain unknown. We demonstrate that Sam68 binds the mRNA for Bcl-x and affects its alternative splicing. Depletion of Sam68 by RNA interference caused accumulation of antiapoptotic Bcl-x(L), whereas its up-regulation increased the levels of proapoptotic Bcl-x(s). Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection. A point mutation in the RNA-binding domain of Sam68 influenced its splicing activity and subnuclear localization. Moreover, coexpression of ASF/SF2 with Sam68, or fusion with an RS domain, counteracted Sam68 splicing activity toward Bcl-x. Finally, Sam68 interacted with heterogenous nuclear RNP (hnRNP) A1, and depletion of hnRNP A1 or mutations that impair this interaction attenuated Bcl-x(s) splicing. Our results indicate that Sam68 plays a role in the regulation of Bcl-x alternative splicing and that tyrosine phosphorylation of Sam68 by Src-like kinases can switch its role from proapoptotic to antiapoptotic in live cells.

scholarly journals The RNA-binding protein DAZL functions as repressor and activator of mRNA translation during oocyte maturation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Cai-Rong Yang ◽  
Gabriel Rajkovic ◽  
Enrico Maria Daldello ◽  
Xuan G. Luong ◽  
Jing Chen ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mrna Translation

scholarly journals A potential role for a novel ZC3H5 complex in regulating mRNA translation in Trypanosoma brucei

2020 ◽  
Vol 295 (42) ◽  
pp. 14291-14304
Author(s):  
Kathrin Bajak ◽  
Kevin Leiss ◽  
Christine Clayton ◽  
Esteban Erben
Keyword(s):  
Gene Expression ◽  
Trypanosoma Brucei ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Affinity Purification ◽  
Critical Role ◽  
Rna Binding Protein ◽  
Mrna Translation

In Trypanosoma brucei and related kinetoplastids, gene expression regulation occurs mostly posttranscriptionally. Consequently, RNA-binding proteins play a critical role in the regulation of mRNA and protein abundance. Yet, the roles of many RNA-binding proteins are not understood. Our previous research identified the RNA-binding protein ZC3H5 as possibly involved in gene repression, but its role in controlling gene expression was unknown. We here show that ZC3H5 is an essential cytoplasmic RNA-binding protein. RNAi targeting ZC3H5 causes accumulation of precytokinetic cells followed by rapid cell death. Affinity purification and pairwise yeast two-hybrid analysis suggest that ZC3H5 forms a complex with three other proteins, encoded by genes Tb927.11.4900, Tb927.8.1500, and Tb927.7.3040. RNA immunoprecipitation revealed that ZC3H5 is preferentially associated with poorly translated, low-stability mRNAs, the 5′-untranslated regions and coding regions of which are enriched in the motif (U/A)UAG(U/A). As previously found in high-throughput analyses, artificial tethering of ZC3H5 to a reporter mRNA or other complex components repressed reporter expression. However, depletion of ZC3H5 in vivo caused only very minor decreases in a few targets, marked increases in the abundances of very stable mRNAs, an increase in monosomes at the expense of large polysomes, and appearance of “halfmer” disomes containing two 80S subunits and one 40S subunit. We speculate that the ZC3H5 complex might be implicated in quality control during the translation of suboptimal open reading frames.

scholarly journals Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation

Science ◽  
2016 ◽  
Vol 353 (6307) ◽  
pp. 1549-1552 ◽  
Author(s):  
A. Kanakkanthara ◽  
K. B. Jeganathan ◽  
J. F. Limzerwala ◽  
D. J. Baker ◽  
M. Hamada ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mrna Translation ◽  
Cyclin A2

Corrigendum to: Cytoplasmic polyadenylation element binding protein 2 (CPEB2) is required for tight-junction assembly for establishment of porcine trophectoderm epithelium

2019 ◽  
Vol 31 (3) ◽  
pp. 632
Author(s):  
Jeongwoo Kwon ◽  
Shuha Park ◽  
Min-Jung Seong ◽  
Inchul Choi ◽  
Nam-Hyung Kim
Keyword(s):  
Tight Junction ◽  
Mrna Stability ◽  
Rna Binding ◽  
Binding Protein ◽  
Mrna Translation ◽  
Coxsackie Virus ◽  
Cytoplasmic Polyadenylation ◽  
Apical Cell Membrane ◽  
Junction Protein ◽  
Element Binding Protein

Cytoplasmic polyadenylation element binding protein (CPEB) is an RNA-binding protein that promotes elongation of poly(A) tails and regulates mRNA translation. CPEB depletion in mammary epithelium is known to disrupt tight-junction (TJ) assembly via mislocalisation of tight junction protein 1 (TJP1), but the role of CPEB in the biological functions associated with TJs has not yet been studied. The objective of this study was to investigate the roles of CPEB2 during porcine parthenote development. CPEB2 was detected in both the nuclei and apical cytoplasm at the 4- and 8-cell stages and was localised to cell–cell contact after the initiation of the morula stage. Its depletion led to retarded blastocyst formation caused by impaired TJ assembly. Moreover, transcription of TJ-associated genes, including TJP1, Coxsackie virus and adenovirus receptor (CXADR) and occludin (OCLN), was not affected, but the corresponding proteins were not properly localised at the apical cell membrane in morulae, suggesting that CPEB2 confers mRNA stability or determines subcellular localisation for translation. Remarkably reduced relative levels of TJP1 transcripts bearing the 3′-untranslated region were noted, indicating that CPEB2 mediates TJP1 mRNA stability. In conclusion, our findings demonstrate that because of its regulation of TJP1, CPEB2 is required for TJ assembly during porcine blastocyst development.

scholarly journals Csde1 cooperates with Strap to control translation of erythroid transcripts

2017 ◽  
Author(s):  
Kat S. Moore ◽  
Nurcan Yagci ◽  
Floris van Alphen ◽  
Alexander B. Meijer ◽  
Peter A.C. ‘t Hoen ◽  
...  
Keyword(s):  
Growth Factors ◽  
Environmental Conditions ◽  
Rna Splicing ◽  
Translational Regulation ◽  
Rna Binding ◽  
Protein Complexes ◽  
Rna Binding Protein ◽  
Mrna Translation ◽  
Hematopoietic Progenitors ◽  
Control Translation

AbstractErythropoiesis is regulated at many levels, including control of mRNA translation. Changing environmental conditions, such as hypoxia, or the availability of nutrients and growth factors, require a rapid response enacted by the enhanced or repressed translation of existing transcripts. Csde1 is an RNA-binding protein required for erythropoiesis and strongly upregulated in erythroblasts relative to other hematopoietic progenitors. The aim of this study is to identify the Csde1-containing protein complexes, and investigate their role in regulating the translation of Csde1-bound transcripts. We show that Strap, also called Unrip, was the protein most strongly associated with Csde1 in erythroblasts. Strap is a WD40 protein involved in signaling and RNA splicing, but its role is unknown when associated with Csde1. Reduced expression of Strap did not alter the pool of transcripts bound by Csde1. Instead, it reduced the mRNA and/or protein expression of several Csde1-bound transcript, that encode for proteins essential for translational regulation during hypoxia, such as Hmbs, eIF4g3 and Pabpc4. Also affected by Strap knockdown were Vim, a Gata-1 target crucial for erythrocyte enucleation, and Elavl1, which stabilizes Gata-1 mRNA. Thus, we found that the Csde1/Strap complex is at the crossroad of multiple pathways governing translation in erythroblasts.

scholarly journals Phosphoregulation provides specificity to biomolecular condensates in the cell cycle and cell polarity

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Therese M. Gerbich ◽  
Grace A. McLaughlin ◽  
Katelyn Cassidy ◽  
Scott Gerber ◽  
David Adalsteinsson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nucleic Acids ◽  
Cell Polarity ◽  
Filamentous Fungus ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Ashbya Gossypii ◽  
Mrna Targets ◽  
Functional Identities

Biomolecular condensation is a way of organizing cytosol in which proteins and nucleic acids coassemble into compartments. In the multinucleate filamentous fungus Ashbya gossypii, the RNA-binding protein Whi3 regulates the cell cycle and cell polarity through forming macromolecular structures that behave like condensates. Whi3 has distinct spatial localizations and mRNA targets, making it a powerful model for how, when, and where specific identities are established for condensates. We identified residues on Whi3 that are differentially phosphorylated under specific conditions and generated mutants that ablate this regulation. This yielded separation of function alleles that were functional for either cell polarity or nuclear cycling but not both. This study shows that phosphorylation of individual residues on molecules in biomolecular condensates can provide specificity that gives rise to distinct functional identities in the same cell.

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