scholarly journals N6-methyladenosine dynamics during early vertebrate embryogenesis

2019 ◽  
Author(s):  
Håvard Aanes ◽  
Dominique Engelsen ◽  
Adeel Manaf ◽  
Endalkachew Ashenafi Alemu ◽  
Cathrine Broberg Vågbø ◽  
...  
Keyword(s):  
Translational Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Degradation ◽  
Translational Efficiency ◽  
Mrna Levels ◽  
Maternal Transcripts ◽  
Post Transcriptional Regulation ◽  
Genome Activation ◽  
Polyadenylated Mrna

AbstractEarly vertebrate embryogenesis is characterized by extensive post-transcriptional regulation during the maternal-to-zygotic transition. The N6-methyladenosine (m6A) modifications on mRNA have been shown to affect both translation and stability of transcripts. Here we investigate the m6A topology during early vertebrate embryogenesis and its association with polyadenylated mRNA levels. The majority (>70%) of maternal transcripts harbor m6A, and there is a substantial increase of m6A in the polyadenylated mRNA fraction between 0 and 2 hours post fertilization. Notably, we find strong associations between m6A, cytoplasmic polyadenylation and translational efficiency prior to zygotic genome activation (ZGA). Interestingly, the relationship between m6A and translation is strongest for peaks located in the 3’UTR, but not overlapping stop codons. Sequence analyses revealed enrichment of motifs for RNA binding proteins involved in translational regulation and RNA degradation. After ZGA, m6A seem to diminish the effect of miR-430 mediated degradation. The reported results improve our understanding of the combinatorial code behind post-transcriptional mRNA regulation during embryonic reprogramming and early differentiation.

scholarly journals An interaction network of RNA-binding proteins involved in Drosophila oogenesis

2020 ◽  
Author(s):  
Prashali Bansal ◽  
Johannes Madlung ◽  
Kristina Schaaf ◽  
Boris Macek ◽  
Fulvia Bono
Keyword(s):  
Translational Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Direct Interaction ◽  
Interaction Network ◽  
Splicing Factors ◽  
Mrna Regulation ◽  
Interaction Partners ◽  
Maternal Transcripts

AbstractDuring Drosophila oogenesis, the localization and translational regulation of maternal transcripts relies on RNA-binding proteins (RBPs). Many of these RBPs localize several mRNAs and may have additional direct interaction partners to regulate their functions. Using immunoprecipitation from whole Drosophila ovaries coupled to mass spectrometry, we examined protein-protein associations of 6 GFP-tagged RBPs expressed at physiological levels. Analysis of the interaction network and further validation in human cells allowed us to identify 26 previously unknown associations, besides recovering several well characterized interactions. We identified interactions between RBPs and several splicing factors, providing links between nuclear and cytoplasmic events of mRNA regulation. Additionally, components of the translational and RNA decay machineries were selectively co-purified with some baits, suggesting a mechanism for how RBPs may regulate maternal transcripts. Given the evolutionary conservation of the studied RBPs, the interaction network presented here provides the foundation for future functional and structural studies of mRNA localization across metazoans.

scholarly journals An Interaction Network of RNA-Binding Proteins Involved in Drosophila Oogenesis

2020 ◽  
Vol 19 (9) ◽  
pp. 1485-1502
Author(s):  
Prashali Bansal ◽  
Johannes Madlung ◽  
Kristina Schaaf ◽  
Boris Macek ◽  
Fulvia Bono
Keyword(s):  
Translational Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Direct Interaction ◽  
Interaction Network ◽  
Splicing Factors ◽  
Mrna Regulation ◽  
Interaction Partners ◽  
Maternal Transcripts

During Drosophila oogenesis, the localization and translational regulation of maternal transcripts relies on RNA-binding proteins (RBPs). Many of these RBPs localize several mRNAs and may have additional direct interaction partners to regulate their functions. Using immunoprecipitation from whole Drosophila ovaries coupled to mass spectrometry, we examined protein-protein associations of 6 GFP-tagged RBPs expressed at physiological levels. Analysis of the interaction network and further validation in human cells allowed us to identify 26 previously unknown associations, besides recovering several well characterized interactions. We identified interactions between RBPs and several splicing factors, providing links between nuclear and cytoplasmic events of mRNA regulation. Additionally, components of the translational and RNA decay machineries were selectively co-purified with some baits, suggesting a mechanism for how RBPs may regulate maternal transcripts. Given the evolutionary conservation of the studied RBPs, the interaction network presented here provides the foundation for future functional and structural studies of mRNA localization across metazoans.

scholarly journals The G4 resolvase RHAU modulates mRNA translation and stability to sustain postnatal heart function and regeneration

2020 ◽  
pp. jbc.RA120.014948
Author(s):  
Mingyang Jiang ◽  
Han Hu ◽  
Ke Zhao ◽  
Ruomin Di ◽  
Xinyi Huang ◽  
...  
Keyword(s):  
Heart Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Heart Function ◽  
Mrna Translation ◽  
Mrna Levels ◽  
Protein Levels ◽  
Post Transcriptional Regulation ◽  
Heart Physiology

Post-transcriptional regulation of mRNA translation and stability is primarily achieved by RNA binding proteins (RBPs), which is of increasing importance for heart function. Furthermore, G-quadruplex (G4) and G4 resolvase activity are involved in a variety of biological processes. However, the role of G4 resolvase activity in heart function remains unknown. The present study aims to investigate the role of RHAU, an RBP with G4 resolvase activity in postnatal heart function through deletion of Rhau in the cardiomyocytes of postnatal mice. RHAU-deficient mice displayed progressive pathological remodeling leading to heart failure and mortality, and impaired neonatal heart regeneration. RHAU ablation reduced the protein levels but enhanced mRNA levels of Yap1 and Hexim1 that are important regulators for heart development and postnatal heart function. Furthermore, RHAU was found to associate with both the 5’- and 3’- UTRs of these genes to destabilize mRNA but to enhance translation. Thus, we have demonstrated the important functions of RHAU in the dual regulation of mRNA translation and stability, which is vital for heart physiology.

scholarly journals Small Trypanosome RNA-Binding Proteins TbUBP1 and TbUBP2 Influence Expression of F-Box Protein mRNAs in Bloodstream Trypanosomes

2007 ◽  
Vol 6 (11) ◽  
pp. 1964-1978 ◽  
Author(s):  
Claudia Hartmann ◽  
Corinna Benz ◽  
Stefanie Brems ◽  
Louise Ellis ◽  
Van-Duc Luu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Degradation ◽  
Rna Recognition Motif ◽  
Mrna Levels ◽  
Control Of Gene Expression ◽  
F Box Protein ◽  
Cyclin F

ABSTRACT In the African trypanosome Trypanosoma brucei nearly all control of gene expression is posttranscriptional; sequences in the 3′-untranslated regions of mRNAs determine the steady-state mRNA levels by regulation of RNA turnover. Here we investigate the roles of two related proteins, TbUBP1 and TbUBP2, containing a single RNA recognition motif, in trypanosome gene expression. TbUBP1 and TbUBP2 are in the cytoplasm and nucleus, comprise ca. 0.1% of the total protein, and are not associated with polysomes or RNA degradation enzymes. Overexpression of TbUBP2 upregulated the levels of several mRNAs potentially involved in cell division, including the CFB1 mRNA, which encodes a protein with a cyclin F-box domain. CFB1 regulation was mediated by the 3′-untranslated region and involved stabilization of the mRNA. Depletion of TbUBP2 and TbUBP1 inhibited growth and downregulated expression of the cyclin F box protein gene CFB2; trans splicing was unaffected. The results of pull-down assays indicated that all tested mRNAs were bound to TbUBP2 or TbUBP1, with some preference for CFB1. We suggest that TbUBP1 and TbUBP2 may be relatively nonspecific RNA-binding proteins and that specific effects of overexpression or depletion could depend on competition between various different proteins for RNA binding.

scholarly journals Dietary restriction induces post-transcriptional regulation of longevity genes

2019 ◽  
Author(s):  
Jarod A. Rollins ◽  
Santina S. Snow ◽  
Pankaj Kapahi ◽  
Aric N. Rogers
Keyword(s):  
Transcriptional Regulation ◽  
Dietary Restriction ◽  
Translational Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Intron Retention ◽  
Translation Efficiency ◽  
Nonsense Mediated Decay ◽  
Longevity Genes ◽  
Post Transcriptional Regulation

AbstractDietary restriction increases lifespan through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of C. elegans subjected to dietary restriction. Transcription of muscle regulatory and structural genes increased, while increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level of translation. Evaluation of post-transcriptional regulation identified putative roles for RNA binding proteins, RNA editing, microRNA, alternative splicing, and nonsense mediated decay in response to nutrient limitation. Using RNA interference, we discovered several differentially expressed genes that regulate lifespan. We also found a compensatory role for translational regulation, which offsets dampened expression of a large subset of transcriptionally downregulated genes. Furthermore, 3’ UTR editing and intron retention increase under dietary restriction and correlate with diminished translation, while trans-spliced genes are refractory to reduced translation efficiency compared to messages with the native 5’ UTR. Finally, we find that smg-6 and smg-7, which are genes governing selection and turnover of nonsense mediated decay targets, are required for increased lifespan under dietary restriction.

scholarly journals Translational regulation of the cell cycle: when, where, how and why?

2011 ◽  
Vol 366 (1584) ◽  
pp. 3638-3652 ◽  
Author(s):  
Iva Kronja ◽  
Terry L. Orr-Weaver
Keyword(s):  
Cell Cycle ◽  
Translational Control ◽  
Translational Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Early Embryogenesis ◽  
Model Organisms ◽  
Translational Efficiency ◽  
Cell Cycle Regulators

Translational regulation contributes to the control of archetypal and specialized cell cycles, such as the meiotic and early embryonic cycles. Late meiosis and early embryogenesis unfold in the absence of transcription, so they particularly rely on translational repression and activation of stored maternal mRNAs. Here, we present examples of cell cycle regulators that are translationally controlled during different cell cycle and developmental transitions in model organisms ranging from yeast to mouse. Our focus also is on the RNA-binding proteins that affect cell cycle progression by recognizing special features in untranslated regions of mRNAs. Recent research highlights the significance of the cytoplasmic polyadenylation element-binding protein (CPEB). CPEB determines polyadenylation status, and consequently translational efficiency, of its target mRNAs in both transcriptionally active somatic cells as well as in transcriptionally silent mature Xenopus oocytes and early embryos. We discuss the role of CPEB in mediating the translational timing and in some cases spindle-localized translation of critical regulators of Xenopus oogenesis and early embryogenesis. We conclude by outlining potential directions and approaches that may provide further insights into the translational control of the cell cycle.

scholarly journals The Role of Pumilio RNA Binding Protein in Plants

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1851
Author(s):  
Sung Un Huh
Keyword(s):  
Abiotic Stresses ◽  
Translational Regulation ◽  
Binding Proteins ◽  
Target Genes ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Specific Binding ◽  
Regulation System ◽  
Translational Efficiency ◽  
Control Target

Eukaryotic organisms have a posttranscriptional/translational regulation system for the control of translational efficiency. RNA binding proteins (RBPs) have been known to control target genes. One type of protein, Pumilio (Pum)/Puf family RNA binding proteins, show a specific binding of 3′ untranslational region (3′ UTR) of target mRNA and function as a post-transcriptional/translational regulator in eukaryotic cells. Plant Pum protein is involved in development and biotic/abiotic stresses. Interestingly, Arabidopsis Pum can control target genes in a sequence-specific manner and rRNA processing in a sequence-nonspecific manner. As shown in in silico Pum gene expression analysis, Arabidopsis and rice Pum genes are responsive to biotic/abiotic stresses. Plant Pum can commonly contribute to host gene regulation at the post-transcriptional/translational step, as can mammalian Pum. However, the function of plant Pum proteins is not yet fully known. In this review, we briefly summarize the function of plant Pum in defense, development, and environmental responses via recent research and bioinformatics data.

scholarly journals Post-transcriptional regulation of inflammation by RNA-binding proteins via cis-elements of mRNAs

2019 ◽  
Vol 166 (5) ◽  
pp. 375-382 ◽  
Author(s):  
Yutaro Uchida ◽  
Tomoki Chiba ◽  
Ryota Kurimoto ◽  
Hiroshi Asahara
Keyword(s):  
Transcriptional Regulation ◽  
Lupus Erythematosus ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Elements ◽  
Translational Efficiency ◽  
Rapid Induction ◽  
Post Transcriptional Regulation

Abstract In human genome, there are approximately 1,500 RNA-binding proteins (RBPs). They can regulate mRNA stability or translational efficiency via ribosomes and these processes are known as ‘post-transcriptional regulation’. Accumulating evidences indicate that post-transcriptional regulation is the determinant of the accurate levels of cytokines mRNAs. While transcriptional regulation of cytokines mRNAs has been well studied and found to be important for the rapid induction of mRNA and regulation of the acute phase of inflammation, post-transcriptional regulation by RBPs is essential for resolving inflammation in the later phase, and their dysfunction may lead to severe autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus. For post-transcriptional regulation, RBPs recognize and directly bind to cis-regulatory elements in 3′ untranslated region of mRNAs such as AU-rich or constitutive decay elements and play various roles. In this review, we summarize the recent findings regarding the role of RBPs in the regulation of inflammation.

scholarly journals Diversity of RNA-Binding Proteins Modulating Post-Transcriptional Regulation of Protein Expression in the Maturing Mammalian Oocyte

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 662 ◽  
Author(s):  
Marie Christou-Kent ◽  
Magali Dhellemmes ◽  
Emeline Lambert ◽  
Pierre F. Ray ◽  
Christophe Arnoult
Keyword(s):  
Transcriptional Regulation ◽  
Translational Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Early Embryo ◽  
Developmental Competence ◽  
Gene Expression Control ◽  
Post Transcriptional Regulation

The oocyte faces a particular challenge in terms of gene regulation. When oocytes resume meiosis at the end of the growth phase and prior to ovulation, the condensed chromatin state prevents the transcription of genes as they are required. Transcription is effectively silenced from the late germinal vesicle (GV) stage until embryonic genome activation (EGA) following fertilisation. Therefore, during its growth, the oocyte must produce the mRNA transcripts needed to fulfil its protein requirements during the active period of meiotic completion, fertilisation, and the maternal-to zygote-transition (MZT). After meiotic resumption, gene expression control can be said to be transferred from the nucleus to the cytoplasm, from transcriptional regulation to translational regulation. Maternal RNA-binding proteins (RBPs) are the mediators of translational regulation and their role in oocyte maturation and early embryo development is vital. Understanding these mechanisms will provide invaluable insight into the oocyte’s requirements for developmental competence, with important implications for the diagnosis and treatment of certain types of infertility. Here, we give an overview of post-transcriptional regulation in the oocyte, emphasising the current knowledge of mammalian RBP mechanisms, and develop the roles of these mechanisms in the timely activation and elimination of maternal transcripts.

scholarly journals Multifunctional RNA-binding proteins influence mRNA abundance and translational efficiency of distinct sets of target genes

2021 ◽  
Vol 17 (12) ◽  
pp. e1009658
Author(s):  
Valentin Schneider-Lunitz ◽  
Jorge Ruiz-Orera ◽  
Norbert Hubner ◽  
Sebastiaan van Heesch
Keyword(s):  
Translational Regulation ◽  
Binding Proteins ◽  
Target Genes ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Translational Efficiency ◽  
Splicing Factors ◽  
Biological Processes ◽  
Differential Affinity

RNA-binding proteins (RBPs) can regulate more than a single aspect of RNA metabolism. We searched for such previously undiscovered multifunctionality within a set of 143 RBPs, by defining the predictive value of RBP abundance for the transcription and translation levels of known RBP target genes across 80 human hearts. This led us to newly associate 27 RBPs with cardiac translational regulation in vivo. Of these, 21 impacted both RNA expression and translation, albeit for virtually independent sets of target genes. We highlight a subset of these, including G3BP1, PUM1, UCHL5, and DDX3X, where dual regulation is achieved through differential affinity for target length, by which separate biological processes are controlled. Like the RNA helicase DDX3X, the known splicing factors EFTUD2 and PRPF8—all identified as multifunctional RBPs by our analysis—selectively influence target translation rates depending on 5’ UTR structure. Our analyses identify dozens of RBPs as being multifunctional and pinpoint potential novel regulators of translation, postulating unanticipated complexity of protein-RNA interactions at consecutive stages of gene expression.

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