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Search results for: DDX6

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#35687120   2022/06/10 To Up

The dsRBP Staufen2 governs RNP assembly of neuronal Argonaute proteins.

Mature microRNAs are bound by a member of the Argonaute (Ago1-4) protein family, forming the core of the RNA-induced silencing complex (RISC). Association of RISC with target mRNAs results in ribonucleoprotein (RNP) assembly involved in translational silencing or RNA degradation. Yet, the dynamics of RNP assembly and its underlying functional implications are unknown. Here, we have characterized the role of the RNA-binding protein Staufen2, a candidate Ago interactor, in RNP assembly. Staufen2 depletion resulted in the upregulation of Ago1/2 and the RISC effector proteins Ddx6 and Dcp1a. This upregulation was accompanied by the displacement of Ago1/2 from processing bodies, large RNPs implicated in RNA storage, and subsequent association of Ago2 with polysomes. In parallel, Staufen2 deficiency decreased global translation and increased dendritic branching. As the observed phenotypes can be rescued by Ago1/2 knockdown, we propose a working model in which both Staufen2 and Ago proteins depend on each other and contribute to neuronal homeostasis.
Janina Ehses, Melina Schlegel, Luise Schröger, Rico Schieweck, Sophia Derdak, Martin Bilban, Karl Bauer, Max Harner, Michael A Kiebler

1203 related Products with: The dsRBP Staufen2 governs RNP assembly of neuronal Argonaute proteins.

2100 1mg101mg5000.1mg100mg101mg50 1000

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#35672286   2022/06/07 To Up

A novel mRNA decay inhibitor abolishes pathophysiological cellular transition.

In cells, mRNA synthesis and decay are influenced by each other, and their balance is altered by either external or internal cues, resulting in changes in cell dynamics. We previously reported that it is important that an array of mRNAs that shape a phenotype are degraded before cellular transitions, such as cellular reprogramming and differentiation. In adipogenesis, the interaction between DDX6 and 4E-T had a definitive impact on the pathway in the processing body (PB). We screened a library of α-helix analogs with an alkaloid-like backbone to identify compounds that inhibit the binding between DDX6 and 4E-T proteins, which occurs between the α-helix of structured and internally disordered proteins. IAMC-00192 was identified as a lead compound. This compound directly inhibited the interaction between DDX6 and 4E-T. IAMC-00192 inhibited the temporal increase in PB formation that occurs during adipogenesis and epithelial-mesenchymal transition (EMT) and significantly suppressed these cellular transitions. In the EMT model, the half-life of preexisting mRNAs in PBs was extended twofold by the compound. The novel inhibitor of RNA decay not only represents a potentially useful tool to analyze in detail the pathological conditions affected by RNA decay and how it regulates the pathological state. The identification of this inhibitor may lead to the discovery of a first-in-class RNA decay inhibitor drug.
Daisuke Kami, Toshimasa Ishizaki, Toshihiko Taya, Akira Katoh, Hiroyuki Kouji, Satoshi Gojo

1348 related Products with: A novel mRNA decay inhibitor abolishes pathophysiological cellular transition.

100uL1 mg100ug Lyophilized50ug20 µl (10 mM)100 assays5 mg100 ul 100ul100 assays20 20

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#35589695   2022/05/19 To Up

RNP components condense into repressive RNP granules in the aging brain.

Cytoplasmic RNP condensates enriched in mRNAs and proteins are found in various cell types and associated with both buffering and regulatory functions. While a clear link has been established between accumulation of aberrant RNP aggregates and progression of aging-related neurodegenerative diseases, the impact of physiological aging on neuronal RNP condensates has never been explored. Through high-resolution imaging, we uncover that RNP components progressively cluster into large yet dynamic granules in the aging Drosophila brain. We further show that age-dependent clustering is caused by an increase in the stoichiometry of the conserved helicase Me31B/DDX6, and requires PKA kinase activity. Finally, our functional analysis reveals that mRNA species recruited to RNP condensates upon aging exhibit age-dependent translational repression, indicating that co-clustering of selected mRNAs and translation regulators into repressive condensates may contribute to the specific post-transcriptional changes in gene expression observed in the course of aging.
Kavya Vinayan Pushpalatha, Mathilde Solyga, Akira Nakamura, Florence Besse

1645 related Products with: RNP components condense into repressive RNP granules in the aging brain.

50 UG50 ul196 tests100 μg

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#35589693   2022/05/19 To Up

RNA supply drives physiological granule assembly in neurons.

Membraneless cytoplasmic condensates of mRNAs and proteins, known as RNA granules, play pivotal roles in the regulation of mRNA fate. Their maintenance fine-tunes time and location of protein expression, affecting many cellular processes, which require complex protein distribution. Here, we report that RNA granules-monitored by DEAD-Box helicase 6 (DDX6)-disassemble during neuronal maturation both in cell culture and in vivo. This process requires neuronal function, as synaptic inhibition results in reversible granule assembly. Importantly, granule assembly is dependent on the RNA-binding protein Staufen2, known for its role in RNA localization. Altering the levels of free cytoplasmic mRNA reveals that RNA availability facilitates DDX6 granule formation. Specifically depleting RNA from DDX6 granules confirms RNA as an important driver of granule formation. Moreover, RNA is required for DDX6 granule assembly upon synaptic inhibition. Together, this data demonstrates how RNA supply favors RNA granule assembly, which not only impacts subcellular RNA localization but also translation-dependent synaptic plasticity, learning, and memory.
Karl E Bauer, Niklas Bargenda, Rico Schieweck, Christin Illig, Inmaculada Segura, Max Harner, Michael A Kiebler

1730 related Products with: RNA supply drives physiological granule assembly in neurons.

200ul200ul100 μg100 μg100ug Lyophilized1 Set1 Set100 μg1 Set

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#35464758   2022/04/14 To Up

Novel piRNA Regulates PIWIL1 to Modulate the Behavior of Placental Trophoblast Cells and Participates in Preeclampsia.

This study is aimed at investigating the role of PIWIL1/piRNA in the development of preeclampsia.
Jing Lin, Ye Zhou, Wei Gu

2891 related Products with: Novel piRNA Regulates PIWIL1 to Modulate the Behavior of Placental Trophoblast Cells and Participates in Preeclampsia.

100 -1.00 flask1x10e7 cells96 assays 1 G

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#35353581   2022/03/30 To Up

eIF4A2 targets developmental potency and histone H3.3 transcripts for translational control of stem cell pluripotency.

Translational control has emerged as a fundamental regulatory layer of proteome complexity that governs cellular identity and functions. As initiation is the rate-limiting step of translation, we carried out an RNA interference screen for key translation initiation factors required to maintain embryonic stem cell (ESC) identity. We identified eukaryotic translation initiation factor 4A2 (eIF4A2) and defined its mechanistic action through ribosomal protein S26-independent and -dependent ribosomes in translation initiation activation of messenger RNAs (mRNAs) encoding pluripotency factors and the histone variant H3.3 with demonstrated roles in maintaining stem cell pluripotency. eIF4A2 also mediates translation initiation activation of Ddx6, which acts together with eIF4A2 to restrict the totipotent two-cell transcription program in ESCs through Zscan4 mRNA degradation and translation repression. Accordingly, knockdown of eIF4A2 disrupts ESC proteome, causing the loss of ESC identity. Collectively, we establish a translational paradigm of the protein synthesis of pluripotency transcription factors and epigenetic regulators imposed on their established roles in controlling pluripotency.
Dan Li, Jihong Yang, Xin Huang, Hongwei Zhou, Jianlong Wang

2258 related Products with: eIF4A2 targets developmental potency and histone H3.3 transcripts for translational control of stem cell pluripotency.

3x10 ug1 x 10^6 cells/vial5 x 10A5 cells/vial100ug30ml500 ml5 x 2 ml3100Tests100ug30ml

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#35107372   2022/02/02 To Up

Host Cellular RNA Helicases Regulate SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the largest RNA genome, approximately 30 kb, among RNA viruses. The DDX DEAD box RNA helicase is a multifunctional protein involved in all aspects of RNA metabolism. Therefore, host RNA helicases may regulate and maintain such a large viral RNA genome. In this study, I investigated the potential role of several host cellular RNA helicases in SARS-CoV-2 infection. Notably, DDX21 knockdown markedly accumulated intracellular viral RNA and viral production, as well as viral infectivity of SARS-CoV-2, indicating that DDX21 strongly restricts the SARS-CoV-2 infection. In addition, MOV10 RNA helicase also suppressed the SARS-CoV-2 infection. In contrast, DDX1, DDX5, and DDX6 RNA helicases were required for SARS-CoV-2 replication. Indeed, SARS-CoV-2 infection dispersed the P-body formation of DDX6 and MOV10 RNA helicases as well as XRN1 exonuclease, while the viral infection did not induce stress granule formation. Accordingly, the SARS-CoV-2 nucleocapsid (N) protein interacted with DDX1, DDX3, DDX5, DDX6, DDX21, and MOV10 and disrupted the P-body formation, suggesting that SARS-CoV-2 N hijacks DDX6 to carry out viral replication. Conversely, DDX21 and MOV10 restricted SARS-CoV-2 infection through an interaction of SARS-CoV-2 N with host cellular RNA helicases. Altogether, host cellular RNA helicases seem to regulate the SARS-CoV-2 infection. SARS-CoV-2 has a large RNA genome, of approximately 30 kb. To regulate and maintain such a large viral RNA genome, host RNA helicases may be involved in SARS-CoV-2 replication. In this study, I have demonstrated that DDX21 and MOV10 RNA helicases limit viral infection and replication. In contrast, DDX1, DDX5, and DDX6 are required for SARS-CoV-2 infection. Interestingly, SARS-CoV-2 infection disrupted P-body formation and attenuated or suppressed stress granule formation. Thus, SARS-CoV-2 seems to hijack host cellular RNA helicases to play a proviral role by facilitating viral infection and replication and by suppressing the host innate immune system.
Yasuo Ariumi

2549 related Products with: Host Cellular RNA Helicases Regulate SARS-CoV-2 Infection.

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#35078859   // To Up

Bone Marrow Surveillance of Pediatric Cancer Survivors Identifies Clones that Predict Therapy-Related Leukemia.

Therapy-related myelodysplastic syndrome and acute leukemias (t-MDS/AL) are a major cause of nonrelapse mortality among pediatric cancer survivors. Although the presence of clonal hematopoiesis (CH) in adult patients at cancer diagnosis has been implicated in t-MDS/AL, there is limited published literature describing t-MDS/AL development in children.
Barbara Spitzer, Kayleigh D Rutherford, Gunes Gundem, Erin M McGovern, Nathan E Millard, Juan E Arango Ossa, Irene Y Cheung, Teng Gao, Max F Levine, Yanming Zhang, Juan S Medina-Martínez, Yi Feng, Ryan N Ptashkin, Kelly L Bolton, Noushin Farnoud, Yangyu Zhou, Minal A Patel, Georgios Asimomitis, Cassidy C Cobbs, Neeman Mohibullah, Kety H Huberman, Maria E Arcilla, Brian H Kushner, Shakeel Modak, Andrew L Kung, Ahmet Zehir, Ross L Levine, Scott A Armstrong, Nai Kong V Cheung, Elli Papaemmanuil

2235 related Products with: Bone Marrow Surveillance of Pediatric Cancer Survivors Identifies Clones that Predict Therapy-Related Leukemia.

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#34929216   2021/12/17 To Up

DEAD/H-box helicases:Anti-viral and pro-viral roles during infections.

DEAD/H-box RNA helicases make the prominent family of helicases super family-2 which take part in almost all RNA-related processes, from initiation of transcription to RNA decay pathways. In addition to these RNA-related activities, in recent years a certain number of these helicases are reported to play important roles in anti-viral immunity through various ways. Along with RLHs, endosomal TLRs, and cytosolic DNA receptors, many RNA helicases including DDX3, DHX9, DDX6, DDX41, DHX33, DDX60, DHX36 and DDX1-DDX21-DHX36 complex act as viral nucleic acid sensors or co-sensors. These helicases mostly follow RLHs-MAVS and STING mediated signaling cascades to trigger induction of type-I interferons and pro-inflammatory cytokines. Many of them also function as downstream adaptor molecules (DDX3), segments of stress and processing bodies (DDX3 and DDX6) or negative regulators (DDX19, DDX24, DDX25, DDX39A and DDX46). On the contrary, many studies indicated that several DEAD/H-box helicases such as DDX1, DDX3, DDX6, DDX24, and DHX9 could be exploited by viruses to evade innate immune responses, suggesting that these helicases seem to have a dual function as anti-viral innate immune mediators and viral replication cofactors. In this review, we summarized the current knowledge on several representative DEAD/H-box helicases, with an emphasis on their functions in innate immunity responses, involved in their anti-viral and pro-viral roles.
Rizwan Ullah, Jia Li, Puxian Fang, Shaobo Xiao, Liurong Fang

2569 related Products with: DEAD/H-box helicases:Anti-viral and pro-viral roles during infections.

100ug/vial100ug/vial100ug/vial100 ug/vial100 µg0.2 mg0.25 mg100ug100ug Lyophilized200 100ug100ug

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