scholarly journals A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Dayana C Farhat ◽  
Matthew W Bowler ◽  
Guillaume Communie ◽  
Dominique Pontier ◽  
Lucid Belmudes ◽  
...  
Keyword(s):  
Regulatory Mechanism ◽  
Developmental Gene ◽  
Regulatory Requirements ◽  
The Core ◽  
Transcriptional Termination ◽  
C Terminus ◽  
Cleavage And Polyadenylation ◽  
Yth Domain ◽  
Host Life ◽  
Shed Light

Correct 3'end processing of mRNAs is one of the regulatory cornerstones of gene expression. In a parasite that must adapt to the regulatory requirements of its multi-host life style, there is a need to adopt additional means to partition the distinct transcriptional signatures of the closely and tandemly-arranged stage specific genes. In this study, we report our findings in T. gondii of an m6A-dependent 3'end polyadenylation serving as a transcriptional barrier at these loci. We identify the core polyadenylation complex within T. gondii and establish CPSF4 as a reader for m6A-modified mRNAs, via a YTH domain within its C-terminus, a feature which is shared with plants. We bring evidence of the specificity of this interaction both biochemically, and by determining the crystal structure at high resolution of the T. gondii CPSF4-YTH in complex with an m6A modified RNA. We show that the loss of m6A, both at the level of its deposition or its recognition was associated with an increase in aberrantly elongated chimeric mRNAs emanating from impaired transcriptional termination, a phenotype previously noticed in the plant model Arabidopsis thaliana. Nanopore direct RNA sequencing shows the occurrence of transcriptional read-through breaching into downstream repressed stage-specific genes, in the absence of either CPSF4 or the m6A RNA methylase components in both T. gondii and A. thaliana. Taken together, our results shed light on an essential regulatory mechanism coupling the pathways of m6A metabolism directly to the cleavage and polyadenylation processes, one that interestingly seem to serve, in both T. gondii and A. thaliana, as a guardian against aberrant transcriptional read-throughs.

scholarly journals A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental genes partitioning in Toxoplasma

2021 ◽  
Author(s):  
Dayana C. Farhat ◽  
Matthew Bowler ◽  
Guillaume Communie ◽  
Dominique Pontier ◽  
Lucid Belmudes ◽  
...  
Keyword(s):  
High Resolution ◽  
Regulatory Mechanism ◽  
List Type ◽  
Regulatory Requirements ◽  
Apicomplexan Parasites ◽  
Transcriptional Termination ◽  
C Terminus ◽  
Cleavage And Polyadenylation ◽  
Host Life ◽  
Shed Light

AbstractCorrect 3’end processing of mRNAs is regarded as one of the regulatory cornerstones of gene expression. In a parasite that must answer to the high regulatory requirements of its multi-host life style, there is a great need to adopt additional means to partition the distinct transcriptional signatures of the closely and tandemly-arranged stage specific genes. In this study, we report on our findings in T. gondii of an m6A-dependent 3’end polyadenylation serving as a transcriptional barrier at these loci. We identify the core polyadenylation complex within T. gondii and establish CPSF4 as a reader for m6A-modified mRNAs, via a YTH domain within its C-terminus, a feature which is shared with plants. We bring evidence of the specificity of this interaction both biochemically, and by determining the crystal structure at high resolution of the T. gondii CPSF4-YTH in complex with an m6A modified RNA. We show that the loss of m6A, both at the level of its deposition or its recognition was associated with an increase in aberrantly elongated chimeric mRNAs emanating from impaired transcriptional termination, a phenotype previously noticed in the plant model Arabidopsis thaliana. We bring Nanopore direct RNA sequencing-based evidence of the occurrence of transcriptional read-through breaching into downstream repressed stage-specific genes, in the absence of either CPSF4 or the m6A RNA methylase components in both T. gondii and A. thaliana. Taken together, our results shed light on an essential regulatory mechanism coupling the pathways of m6A metabolism directly to the cleavage and polyadenylation processes, one that interestingly seem to serve, in both T. gondii and A. thaliana, as a guardian against aberrant transcriptional read-throughs.Highlightsm6A is recognized in apicomplexan and plants by CPSF4, a member of the cleavage and polyadenylation complex machinery.The structural insight behind the specificity of the binding of m6A by the CPSF4 YTH subunit are solved by high resolution crystal structures.The m6A-driven 3’end polyadenylation pathway protects transcriptome integrity by restricting transcriptional read-throughs and RNA chimera formation in apicomplexan parasites and plants.

scholarly journals Scaffold subunits support associated subunit assembly in the Chlamydomonas ciliary nexin–dynein regulatory complex

2019 ◽  
Vol 116 (46) ◽  
pp. 23152-23162 ◽  
Author(s):  
Long Gui ◽  
Kangkang Song ◽  
Douglas Tritschler ◽  
Raqual Bower ◽  
Si Yan ◽  
...  
Keyword(s):  
Electron Tomography ◽  
Wild Type ◽  
Core Complex ◽  
The Core ◽  
C Terminus ◽  
Cryo Electron Tomography ◽  
Regulatory Complex ◽  
Cilia And Flagella ◽  
Linker Domain ◽  
Shed Light

The nexin–dynein regulatory complex (N-DRC) in motile cilia and flagella functions as a linker between neighboring doublet microtubules, acts to stabilize the axonemal core structure, and serves as a central hub for the regulation of ciliary motility. Although the N-DRC has been studied extensively using genetic, biochemical, and structural approaches, the precise arrangement of the 11 (or more) N-DRC subunits remains unknown. Here, using cryo-electron tomography, we have compared the structure of Chlamydomonas wild-type flagella to that of strains with specific DRC subunit deletions or rescued strains with tagged DRC subunits. Our results show that DRC7 is a central linker subunit that helps connect the N-DRC to the outer dynein arms. DRC11 is required for the assembly of DRC8, and DRC8/11 form a subcomplex in the proximal lobe of the linker domain that is required to form stable contacts to the neighboring B-tubule. Gold labeling of tagged subunits determines the precise locations of the previously ambiguous N terminus of DRC4 and C terminus of DRC5. DRC4 is now shown to contribute to the core scaffold of the N-DRC. Our results reveal the overall architecture of N-DRC, with the 3 subunits DRC1/2/4 forming a core complex that serves as the scaffold for the assembly of the “functional subunits,” namely DRC3/5–8/11. These findings shed light on N-DRC assembly and its role in regulating flagellar beating.

Risk Assessment of Core Banking System Replacement based on ISACA Framework

2014 ◽  
Vol 1 (1) ◽  
pp. 35-45
Author(s):  
Fenty Simanjuntak ◽  
Bobby Suryajaya
Keyword(s):  
Risk Assessment ◽  
Banking System ◽  
Residual Risk ◽  
Project Teams ◽  
Third Party ◽  
Project Delivery ◽  
Business Growth ◽  
Regulatory Requirements ◽  
The Core ◽  
Medium Risk

Many banks are looking for a better core banking system to support their business growth with a more efficient and flexible core banking system to improve their sales and services in the competitive market and to fulfill regulatory requirements. The decision of replacing the legacy core banking system is difficult due to the high IT investment cost required for banks because they are also trying to cut costs. But maintaining the legacy system is costly in terms of upgrade. Changing the core banking system is also a difficult process and increases risks. To have a successful Core Banking System implementation, risk assessment is required to be performed prior to starting any activities. The assessment can help project teams to identify the risks and then to mitigate the risks as part of the plan. In this research the Core Banking System replacement risks were assessed based on ISACA Framework for IT Risk. Fourteen risk scenarios related to Core Banking System Replacement were identified. The high and medium rated inherent risks can become medium and low residual risk after assessment by putting the relevant control in place. The result proves that by adding mitigation plan it will help to mitigate the Residual Risk to become low risk. There are still three residual risk which categorized as medium risk and should be further mitigated they are Software Implementation, Project Delivery and Selection/Performance of Third Party Suppliers. It is also found that COBIT 5 has considered some specific process capabilities that can be used to improve the processes to mitigate the medium risks.

scholarly journals Contextualization of the Bioeconomy Concept through Its Links with Related Concepts and the Challenges Facing Humanity

2021 ◽  
Vol 13 (14) ◽  
pp. 7746
Author(s):  
Leire Barañano ◽  
Naroa Garbisu ◽  
Itziar Alkorta ◽  
Andrés Araujo ◽  
Carlos Garbisu
Keyword(s):  
Environmental Economics ◽  
Green Economy ◽  
Added Value ◽  
Economic Activities ◽  
Biological Resources ◽  
Beneficial Effects ◽  
The Core ◽  
Points Of View ◽  
Broad Interpretation ◽  
Shed Light

The concept of bioeconomy is a topic of debate, confusion, skepticism, and criticism. Paradoxically, this is not necessarily a negative thing as it is encouraging a fruitful exchange of information, ideas, knowledge, and values, with concomitant beneficial effects on the definition and evolution of the bioeconomy paradigm. At the core of the debate, three points of view coexist: (i) those who support a broad interpretation of the term bioeconomy, through the incorporation of all economic activities based on the production and conversion of renewable biological resources (and organic wastes) into products, including agriculture, livestock, fishing, forestry and similar economic activities that have accompanied humankind for millennia; (ii) those who embrace a much narrower interpretation, reserving the use of the term bioeconomy for new, innovative, and technologically-advanced economic initiatives that result in the generation of high-added-value products and services from the conversion of biological resources; and (iii) those who stand between these two viewpoints. Here, to shed light on this debate, a contextualization of the bioeconomy concept through its links with related concepts (biotechnology, bio-based economy, circular economy, green economy, ecological economics, environmental economics, etc.) and challenges facing humanity today is presented.

scholarly journals Conformation Study of Dual Stimuli-Responsive Core-Shell Diblock Polymer Brushes

Polymers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1084
Author(s):  
Kaimin Chen ◽  
Lan Cao ◽  
Ying Zhang ◽  
Kai Li ◽  
Xue Qin ◽  
...  
Keyword(s):  
Polymer Brushes ◽  
Core Shell ◽  
Stimuli Responsive ◽  
Research Topics ◽  
Design And Synthesis ◽  
Mild Conditions ◽  
The Core ◽  
Responsive Polymer ◽  
Stimuli Responsive Polymer ◽  
Shed Light

Stimuli-responsive nanoparticles are among the most popular research topics. In this study, two types of core-shell (polystyrene with a photoiniferter (PSV) as the core and diblock as the shell) polymer brushes (PSV@PNIPA-b-PAA and PSV@PAA-b-PNIPA) were designed and prepared using surface-initiated photoiniferter-mediated polymerization (SI-PIMP). Moreover, their pH- and temperature-stimuli responses were explored by dynamic light scattering (DLS) and turbidimeter under various conditions. The results showed that the conformational change was determined on the basis of the competition among electrostatic repulsion, hydrophobic interaction, hydrogen bonding, and steric hindrance, which was also confirmed by protein adsorption experiments. These results are not only helpful for the design and synthesis of stimuli-responsive polymer brushes but also shed light on controlled protein immobilization under mild conditions.

scholarly journals Can evolutionary thinking shed light on gender diversity?

2019 ◽  
Vol 25 (6) ◽  
pp. 351-362 ◽  
Author(s):  
Bernadette Wren ◽  
John Launer ◽  
Michael J. Reiss ◽  
Annie Swanepoel ◽  
Graham Music
Keyword(s):  
Gender Identity ◽  
Gender Diversity ◽  
Medical Intervention ◽  
List Type ◽  
Sex And Gender ◽  
Medical Interventions ◽  
The Core ◽  
Causal Pathways ◽  
And Gender ◽  
Shed Light

SUMMARYIssues of sexual reproduction lie at the core of evolutionary thinking, which often places an emphasis on how individuals attempt to maximise the number of successful offspring that they can produce. At first sight, it may therefore appear that individuals who opt for gender-affirming medical interventions are acting in ways that are evolutionarily disadvantageous. However, there are persuasive hypotheses that might make sense of such choices in evolutionary terms and we explore these here. It is premature to claim knowledge of the extent to which evolutionary arguments can usefully be applied to issues of gender identity, although worth reflecting on the extent to which nature tends towards diversity in matters of sex and gender. The importance of acknowledging and respecting different views in this domain, as well as recognising both the uncertainty and likely multiplicity of causal pathways, has implications for clinicians. We make some suggestions about how clinicians might best respond when faced with requests from patients in this area.LEARNING OBJECTIVESAfter reading this article you will be able to:•understand evolutionary arguments about diversity in human gender identity•identify strengths and weaknesses in evolutionary arguments applied to transgender issues•appreciate the range and diversity of gender experience and gender expression among people who present to specialist gender services, as well as the likely complexities of their reasons for requesting medical intervention.

scholarly journals فکر اقبال کی تشکیل میں ملائکہ مقربین کے کرداروں کی معنویت (اردو نظموں کی روشنی میں)

2017 ◽  
pp. 21-31
Author(s):  
Dr. Anwar ul Haq
Keyword(s):  
Full Detail ◽  
The Core ◽  
Islamic Thought ◽  
Core Subjects ◽  
Islamic Values ◽  
Shed Light

The characters of angels(Jibrael, Izrael ,Israfeel and Rizwan) in the poetry of Iqbal are capable of great virtual importance. Through these supernatural characters, Iqbal has successfully conveyed his thoughts in a very impressive and artistic way. He was against the slavery and used these characters in his poetry to motivate Muslims to obtain the virtual goal of freedom. These characters are also the symbols of Islamic values and thoughts. They successfully convey the core subjects of Islamic thought. The researcher has shed light on this specific angle of Iqbal’s poetry in full detail.

scholarly journals Cellular location and activity of Escherichia coli RecG proteins shed light on the function of its structurally unresolved C-terminus

2014 ◽  
Vol 42 (9) ◽  
pp. 5702-5714 ◽  
Author(s):  
Amy L. Upton ◽  
Jane I. Grove ◽  
Akeel A. Mahdi ◽  
Geoffrey S. Briggs ◽  
David S. Milner ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cellular Location ◽  
C Terminus ◽  
Shed Light

A conserved motif within the flexible C-terminus of the translational regulator 4E-BP is required for tight binding to the mRNA cap-binding protein eIF4E

2011 ◽  
Vol 441 (1) ◽  
pp. 237-245 ◽  
Author(s):  
Keum Soon Paku ◽  
Yu Umenaga ◽  
Tsunego Usui ◽  
Ai Fukuyo ◽  
Atsuo Mizuno ◽  
...  
Keyword(s):  
Amino Acid ◽  
Binding Protein ◽  
Tight Binding ◽  
Terminal Region ◽  
Dynamics Simulation ◽  
Initiation Factor ◽  
Binding Region ◽  
The Core ◽  
C Terminus ◽  
Conserved Region

Although the central α-helical Y(X)4LΦ motif (X, variable amino acid; Φ, hydrophobic amino acid) of the translational regulator 4E-BP [eIF (eukaryotic initiation factor) 4E-binding protein] is the core binding region for the mRNA cap-binding protein eIF4E, the functions of its N- and C-terminal flexible regions for interaction with eIF4E remain to be elucidated. To identify the role for the C-terminal region in such an interaction, the binding features of full-length and sequential C-terminal deletion mutants of 4E-BPn (n=1–3) subtypes were investigated by SPR (surface plasmon resonance) analysis and ITC (isothermal titration calorimetry). Consequently, the conserved PGVTS/T motif within the C-terminal region was shown to act as the second binding region and to play an important role in the tight binding to eIF4E. The 4E-BP subtypes increased the association constant with eIF4E by approximately 1000-fold in the presence of this conserved region compared with that in the absence of this region. The sequential deletion of this conserved region in 4E-BP1 showed that deletion of Val81 leads to a considerable decrease in the binding ability of 4E-BP. Molecular dynamics simulation suggested that the conserved PGVTS/T region functions as a kind of paste, adhering the root of both the eIF4E N-terminal and 4E-BP C-terminal flexible regions through a hydrophobic interaction, where valine is located at the crossing position of both flexible regions. It is concluded that the conserved PGVTS/T motif within the flexible C-terminus of 4E-BP plays an auxiliary, but indispensable, role in strengthening the binding of eIF4E to the core Y(X)4LΦ motif.

scholarly journals The Sad1-UNC-84 homology domain in Mps3 interacts with Mps2 to connect the spindle pole body with the nuclear envelope

2006 ◽  
Vol 174 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Sue L. Jaspersen ◽  
Adriana E. Martin ◽  
Galina Glazko ◽  
Thomas H. Giddings ◽  
Garry Morgan ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Integral Membrane Proteins ◽  
Microtubule Nucleation ◽  
The Core ◽  
Pole Body ◽  
C Terminus ◽  
Bridge Structures ◽  
Sun Domain

The spindle pole body (SPB) is the sole site of microtubule nucleation in Saccharomyces cerevisiae; yet, details of its assembly are poorly understood. Integral membrane proteins including Mps2 anchor the soluble core SPB in the nuclear envelope. Adjacent to the core SPB is a membrane-associated SPB substructure known as the half-bridge, where SPB duplication and microtubule nucleation during G1 occurs. We found that the half-bridge component Mps3 is the budding yeast member of the SUN protein family (Sad1-UNC-84 homology) and provide evidence that it interacts with the Mps2 C terminus to tether the half-bridge to the core SPB. Mutants in the Mps3 SUN domain or Mps2 C terminus have SPB duplication and karyogamy defects that are consistent with the aberrant half-bridge structures we observe cytologically. The interaction between the Mps3 SUN domain and Mps2 C terminus is the first biochemical link known to connect the half-bridge with the core SPB. Association with Mps3 also defines a novel function for Mps2 during SPB duplication.

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