scholarly journals CBX4 regulates long-form thymic stromal lymphopoietin-mediated airway inflammation through SUMOylation in HDM-induced asthma

2021 ◽  
Author(s):  
Shixiu Liang ◽  
Zicong Zhou ◽  
Zili Zhou ◽  
Jieyi Liu ◽  
Hangming Dong ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Airway Epithelium ◽  
Rna Binding ◽  
Short Form ◽  
Mrna Translation ◽  
Therapeutic Agents ◽  
Thymic Stromal Lymphopoietin ◽  
Long Form ◽  
Th2 Inflammation ◽  
Novel Target

Rationale: Thymic stromal lymphopoietin (TSLP) is present in two distinct isoforms, short-form (sfTSLP) and long-form (lfTSLP). lfTSLP promotes inflammation while sfTSLP inhibits inflammation in allergic asthma. However, little is known about the regulation of lfTSLP and sfTSLP during allergic attack in asthma airway epithelium. Methods and Results: Here, we report that SUMOylation was enhanced in HDM-induced allergic asthma airway epithelium. Inhibition of SUMOylation significantly alleviated airway Th2 inflammation and lfTSLP expression. Mechanistically, CBX4, a SUMOylation E3 ligase, enhanced lfTSLP, but not sfTSLP, mRNA translation through the RNA binding protein, MEX-3B. MEX-3B promoted lfTSLP translation through binding of its KH domains to the lfTSLP mRNA. Furthermore, CBX4 regulated MEX-3B transcription in HBE through enhancing SUMOylation levels of the transcription factor, TFII-I. Conclusion: We demonstrate an important mechanism whereby CBX4 promotes MEX-3B transcription through enhancing TFII-I SUMOylation, and MEX-3B enhances the expression of lfTSLP through binding to the lfTSLP mRNA and promoting its translation. Our findings uncover a novel target of CBX4 for therapeutic agents to lfTSLP-mediated asthma.

scholarly journals The ALBA RNA-binding proteins function redundantly to promote growth and flowering in Arabidopsis

2019 ◽  
Author(s):  
Naiqi Wang ◽  
Meachery Jalajakumari ◽  
Thomas Miller ◽  
Mohsen Asadi ◽  
Anthony A Millar
Keyword(s):  
Gene Expression ◽  
Protein Function ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Short Form ◽  
Expression Patterns ◽  
Wild Type ◽  
Long Form ◽  
Mrna Binding

AbstractRNA-binding proteins (RBPs) are critical regulators of gene expression, but have been poorly studied relative to other classes of gene regulators. Recently, mRNA-interactome capture identified many Arabidopsis RBPs of unknown function, including a family of ALBA domain containing proteins. Arabidopsis has three short-form ALBA homologues (ALBA1-3) and three long-form ALBA homologues (ALBA4-6), both of which are conserved throughout the plant kingdom. Despite this ancient origin, ALBA-GUS translational fusions of ALBA1, ALBA2, ALBA4, and ALBA5 had indistinguishable expression patterns, all being preferentially expressed in young, rapidly dividing tissues. Likewise, all four ALBA proteins had indistinguishable ALBA-GFP subcellular localizations in roots, all being preferentially located to the cytoplasm, consistent with being mRNA-binding. Genetic analysis demonstrated redundancy within the long-form ALBA family members; in contrast to single alba mutants that all appeared wild-type, a triple alba456 mutant had slower rosette growth and a strong delay in flowering-time. RNA-sequencing found most differentially expressed genes in alba456 were related to metabolism, not development. Additionally, changes to the alba456 transcriptome were subtle, suggesting ALBA4-6 participates in a process that does not strongly affect transcriptome composition. Together, our findings demonstrate that ALBA protein function is highly redundant, and is essential for proper growth and flowering in Arabidopsis.HighlightThe RNA-binding ALBA proteins have indistinguishable expression patterns and subcellular localizations in Arabidopsis, acting redundantly to promote growth and flowering via a mechanism that does not strongly affect transcriptome composition.

scholarly journals Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Si-Hang Wang ◽  
Ya-Gang Zuo
Keyword(s):  
Atopic Dermatitis ◽  
Lupus Erythematosus ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Short Form ◽  
Thymic Stromal Lymphopoietin ◽  
Immunomodulatory Activity ◽  
Immune Mediated ◽  
Long Form ◽  
Pleiotropic Properties

Thymic stromal lymphopoietin (TSLP) was initially demonstrated to be critical in regulating inflammatory responses among various allergic disorders (such as atopic dermatitis, food allergy, and asthma). Although two isoforms (short form and long form) of TSLP have been demonstrated in human tissues, the long form of TSLP (lfTSLP) is strongly implicated in the pathogenesis of allergies and cutaneous immune-mediated diseases. The immunomodulatory activity of lfTSLP varies widely, driving T helper (Th) cells polarizing Th2 and Th17 immune responses and inducing itch. Moreover, lfTSLP is closely associated with skin fibrosis, epidermal hyperplasia, angiogenesis, and homeostatic tolerogenic regulations. This review highlights significant progress from experimental and clinical studies on lfTSLP in cutaneous immune-mediated diseases (atopic dermatitis, psoriasis, bullous pemphigoid, systemic sclerosis, chronic spontaneous urticaria, Behçet’s disease, vitiligo, rosacea, systemic lupus erythematosus, and alopecia areata). We also offer original insights into the pleiotropic properties of the cytokine TSLP in various pathophysiological conditions, with significant clinical implications of TSLP-targeted therapies for immune-mediated skin diseases in the future.

scholarly journals RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA

2020 ◽  
pp. jbc.RA120.014894
Author(s):  
Ravi Kumar ◽  
Dipak Kumar Poria ◽  
Partho Sarothi Ray
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Suppressor Gene ◽  
Cooperative Action ◽  
Translation Repression

Post-transcriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a pro-inflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) HuR in response to LPS stimulation, but the role of other regulatory factors remain unknown. Here we report that the RBP Lupus antigen (La) interacts with the 3’UTR of PDCD4 mRNA and prevents miR-21-mediated translation repression. While LPS causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.

scholarly journals The Role of Translation Initiation Regulation in Haematopoiesis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Godfrey Grech ◽  
Marieke von Lindern
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Translational Control ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Translation Control ◽  
Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

scholarly journals Chemokine Transcripts as Targets of the RNA-Binding Protein HuR in Human Airway Epithelium

2011 ◽  
Vol 186 (4) ◽  
pp. 2482-2494 ◽  
Author(s):  
Jinshui Fan ◽  
Faoud T. Ishmael ◽  
Xi Fang ◽  
Allen Myers ◽  
Chris Cheadle ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Human Airway ◽  
Human Airway Epithelium

scholarly journals Pseudogene ACTBP2 increases blood–brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aβ1–42 microenvironment

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qianshuo Liu ◽  
Xiaobai Liu ◽  
Defeng Zhao ◽  
Xuelei Ruan ◽  
Rui Su ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Vital Role ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Novel Target ◽  
And Function

AbstractThe blood–brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer’s disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ1–42 microenvironment. BBB model treated with Aβ1–42 for 48 h were used to simulate Aβ-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aβ1–42 microenvironment. In Aβ1–42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3′UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aβ1–42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aβ1–42 microenvironment, which may provide a novel target for the therapy of AD.

Preliminary Validation of a Short-Form Version of the Attachment Style Questionnaire for Use in Clinical Rehabilitation Counseling Research and Practice

2017 ◽  
Vol 61 (4) ◽  
pp. 205-216 ◽  
Author(s):  
Kanako Iwanaga ◽  
John Blake ◽  
Rana Yaghmaian ◽  
Emre Umucu ◽  
Fong Chan ◽  
...  
Keyword(s):  
Attachment Style ◽  
Sense Of Coherence ◽  
Short Form ◽  
Rehabilitation Counseling ◽  
People With Disabilities ◽  
Satisfaction With Life Scale ◽  
Research And Practice ◽  
Cord Injury ◽  
Long Form ◽  
Attachment Style Questionnaire

The purpose of this study was to develop and validate a short-form version of the Attachment Style Questionnaire (ASQ) in people with disabilities. The construction sample consisted of 108 participants recruited from spinal cord injury (SCI) advocacy organizations. The cross-validation sample comprised 140 individuals with traumatic injuries recruited from a rehabilitation hospital. Measures administered were the ASQ, Trait Hope Scale, Sense of Coherence Scale, and Satisfaction With Life Scale. Results showed that the three subscales of secure, anxious, and avoidant attachment from the short-form ASQ had high correlations with the three subscales from the long-form ASQ. The reliability of the subscales for the short-form ASQ was adequate and similar to the long-form ASQ. Both the short- and long-form ASQ subscales were found to correlate with hope, sense of coherence, and subjective well-being in the expected theoretical directions. Confirmatory factor analysis also supported the three-factor measurement structure of the short-form ASQ. This study provides evidence to support the psychometric properties of the abbreviated ASQ in people with disabilities. The short-form version of the ASQ is a brief, reliable, and psychometrically sound measure of attachment that can be used in clinical rehabilitation counseling research and practice.

scholarly journals Multidimensional measure of immigrant integration

2018 ◽  
Vol 115 (45) ◽  
pp. 11483-11488 ◽  
Author(s):  
Niklas Harder ◽  
Lucila Figueroa ◽  
Rachel M. Gillum ◽  
Dominik Hangartner ◽  
David D. Laitin ◽  
...  
Keyword(s):  
Immigration Policy ◽  
Fundamental Problem ◽  
Short Form ◽  
Scientific Progress ◽  
Immigrant Integration ◽  
Multidimensional Measure ◽  
Long Form ◽  
Empirical Performance ◽  
Integration Of Immigrants ◽  
Levels Of Integration

The successful integration of immigrants into a host country’s society, economy, and polity has become a major issue for policymakers in recent decades. Scientific progress in the study of immigrant integration has been hampered by the lack of a common measure of integration, which would allow for the accumulation of knowledge through comparison across studies, countries, and time. To address this fundamental problem, we propose the Immigration Policy Lab (IPL) Integration Index as a pragmatic and multidimensional measure of immigrant integration. The measure, both in the 12-item short form (IPL-12) and the 24-item long form (IPL-24), captures six dimensions of integration: psychological, economic, political, social, linguistic, and navigational. The measure can be used across countries, over time, and across different immigrant groups and can be administered through short questionnaires available in different modes. We report on four surveys we conducted to evaluate the empirical performance of our measure. The tests reveal that the measure distinguishes among immigrant groups with different expected levels of integration and also correlates with well-established predictors of integration.

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