Unmasking the role of the 3? UTR in the cytoplasmic polyadenylation and translational regulation of maternal mRNAs

BioEssays ◽  
1994 ◽  
Vol 16 (8) ◽  
pp. 533-535 ◽  
Author(s):  
Michael Wormington
Keyword(s):  
Translational Regulation ◽  
Cytoplasmic Polyadenylation ◽  
Maternal Mrnas

scholarly journals Embryonic poly(A)-binding protein (ePAB) phosphorylation is required for Xenopus oocyte maturation

2012 ◽  
Vol 445 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Kyle Friend ◽  
Matthew Brook ◽  
F. Betül Bezirci ◽  
Michael D. Sheets ◽  
Nicola K. Gray ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Binding Protein ◽  
Xenopus Laevis Oocytes ◽  
Protein Activity ◽  
Cytoplasmic Polyadenylation ◽  
Post Translational Modifications ◽  
Maternal Mrnas ◽  
Insight Into

Oocyte maturation and early embryonic development require the cytoplasmic polyadenylation and concomitant translational activation of stored maternal mRNAs. ePAB [embryonic poly(A)-binding protein, also known as ePABP and PABPc1-like] is a multifunctional post-transcriptional regulator that binds to poly(A) tails. In the present study we find that ePAB is a dynamically modified phosphoprotein in Xenopus laevis oocytes and show by mutation that phosphorylation at a four residue cluster is required for oocyte maturation. We further demonstrate that these phosphorylations are critical for cytoplasmic polyadenylation, but not for ePAB's inherent ability to promote translation. Our results provide the first insight into the role of post-translational modifications in regulating PABP protein activity in vivo.

Sequential waves of polyadenylation and deadenylation define a translation circuit that drives meiotic progression

2008 ◽  
Vol 36 (4) ◽  
pp. 665-670 ◽  
Author(s):  
Eulàlia Belloc ◽  
Maria Piqué ◽  
Raúl Méndez
Keyword(s):  
Untranslated Region ◽  
Translational Regulation ◽  
Feedback Loops ◽  
Quiescent State ◽  
Cytoplasmic Polyadenylation ◽  
Meiotic Progression ◽  
Negative Feedback Loops ◽  
Positive And Negative Feedback ◽  
Maternal Mrnas ◽  
Combinatorial Code

The maternal mRNAs that drive meiotic progression in oocytes contain short poly(A) tails and it is only when these tails are elongated that translation takes place. Cytoplasmic polyadenylation requires two elements in the 3′-UTR (3′-untranslated region), the hexanucleotide AAUAAA and the CPE (cytoplasmic polyadenylation element), which also participates in the transport and localization, in a quiescent state, of its targets. However, not all CPE-containing mRNAs are activated at the same time during the cell cycle, and polyadenylation is temporally and spatially regulated during meiosis. We have recently deciphered a combinatorial code that can be used to qualitatively and quantitatively predict the translational behaviour of CPE-containing mRNAs. This code defines positive and negative feedback loops that generate waves of polyadenylation and deadenylation, creating a circuit of mRNA-specific translational regulation that drives meiotic progression.

scholarly journals Specificity of RNA Binding by CPEB: Requirement for RNA Recognition Motifs and a Novel Zinc Finger

1998 ◽  
Vol 18 (2) ◽  
pp. 685-693 ◽  
Author(s):  
Laura E. Hake ◽  
Raul Mendez ◽  
Joel D. Richter
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Rna Recognition ◽  
Cytoplasmic Polyadenylation ◽  
Functional Motif ◽  
Rna Recognition Motifs ◽  
Amino Terminal ◽  
Terminal Amino ◽  
Maternal Mrnas ◽  
Recognition Motifs

ABSTRACT CPEB is an RNA binding protein that interacts with the maturation-type cytoplasmic polyadenylation element (CPE) (consensus UUUUUAU) to promote polyadenylation and translational activation of maternal mRNAs in Xenopus laevis. CPEB, which is conserved from mammals to invertebrates, is composed of three regions: an amino-terminal portion with no obvious functional motif, two RNA recognition motifs (RRMs), and a cysteine-histidine region that is reminiscent of a zinc finger. In this study, we investigated the physical properties of CPEB required for RNA binding. CPEB can interact with RNA as a monomer, and phosphorylation, which modifies the protein during oocyte maturation, has little effect on RNA binding. Deletion mutations of CPEB have been overexpressed inEscherichia coli and used in a series of RNA gel shift experiments. Although a full-length and a truncated CPEB that lacks 139 amino-terminal amino acids bind CPE-containing RNA avidly, proteins that have had either RRM deleted bind RNA much less efficiently. CPEB that has had the cysteine-histidine region deleted has no detectable capacity to bind RNA. Single alanine substitutions of specific cysteine or histidine residues within this region also abolish RNA binding, pointing to the importance of this highly conserved domain of the protein. Chelation of metal ions by 1,10-phenanthroline inhibits the ability of CPEB to bind RNA; however, RNA binding is restored if the reaction is supplemented with zinc. CPEB also binds other metals such as cobalt and cadmium, but these destroy RNA binding. These data indicate that the RRMs and a zinc finger region of CPEB are essential for RNA binding.

IL-15: the role of translational regulation in their expression

1996 ◽  
Vol 59 (4) ◽  
pp. 476-480 ◽  
Author(s):  
R. N. Bamford ◽  
A. P. Battiata ◽  
T. A. Waldmann
Keyword(s):  
Translational Regulation

scholarly journals The 3’UTR of the orb2 gene encoding the Drosophila CPEB translation factor plays a critical role in spermatogenesis

2020 ◽  
Author(s):  
Rudolf A. Gilmutdinov ◽  
Eugene N. Kozlov ◽  
Ludmila V. Olenina ◽  
Alexei A. Kotov ◽  
Justinn Barr ◽  
...  
Keyword(s):  
Deletion Mutant ◽  
Critical Role ◽  
Self Regulation ◽  
Biological Processes ◽  
Apparent Effect ◽  
Gene Encoding ◽  
Cytoplasmic Polyadenylation ◽  
Polarized Cells ◽  
Biological Context

AbstractCPEB proteins are conserved translation regulators involved in multiple biological processes. One of these proteins in Drosophila, Orb2, is a principal player in spermatogenesis. It is required for meiosis and spermatid differentiation. During the later process orb2 mRNAs and proteins are localized within the developing spermatid. To evaluate the role of orb2 mRNA 3’UTR in spermatogenesis, we used the CRISPR/Cas9 system to generate a deletion of the orb2 3’UTR, orb2R. This deletion disrupts the process of spermatid differentiation, but has no apparent effect on meiosis. While this deletion appears to destabilize the orb2 mRNA and reduce the levels of Orb2 protein, this is not the primary cause of the differentiation defects. Instead, differentiation appears to be disrupted because orb2 mRNAs and proteins are not properly localized within the differentiating spermatids. Other transcripts and proteins involved in spermatogenesis are also mislocalized in orb2R spermatids.Author summaryThe conserved family of cytoplasmic polyadenylation element binding (CPEB) proteins can activate or repress translation of target mRNAs, depending on the specific biological context, through interaction with special cytoplasmic polyadenylation element (CPE) sequences. These proteins function mainly in highly polarized cells. Orb2, one of the two Drosophila melanogaster CPEB proteins, is predominantly expressed in the testes and is crucial for spermatogenesis. The 3’UTR of orb2 transcript contains multiple CPE-like motifs, which is indicative of orb2 self-regulation. We have generated a deletion that removes the greater portion of 3’UTR. While this deletion causes a reduction in the levels of orb2 mRNA and the protein, this does not appear to be responsible for the defects in spermatogenesis observed in the deletion mutant. Instead, it is the mislocalization of the mRNA and protein in the developing spermatids.

scholarly journals Role of CDK1 in Translational Regulation in the M-Phase

2020 ◽  
Author(s):  
Jaroslav Kalous ◽  
Denisa Jansova ◽  
Andrej Susor
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Translational Regulation ◽  
Gene Expression Regulation ◽  
Translational Initiation ◽  
Initiation Factors ◽  
Cellular Events ◽  
M Phase ◽  
Mitosis And Meiosis

Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of active CDK1 in the initiation and elongation steps of protein synthesis in eukaryotes. During its activation CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent cell cycle/M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1, to optimize temporal synthesis of proteins to sustain division-related processes: mitosis and cytokinesis.

scholarly journals Role of the RNA2 3′ non-translated region of Blackcurrant reversion nepovirus in translational regulation

Virology ◽  
2006 ◽  
Vol 354 (1) ◽  
pp. 178-191 ◽  
Author(s):  
Alexey Karetnikov ◽  
Mika Keränen ◽  
Kirsi Lehto
Keyword(s):  
Translational Regulation
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