更新于：2024-05-01

HNRNPD

heterogeneous nuclear ribonucleoprotein D

更新于：2024-05-01

基本信息

别名

AU-rich element RNA-binding protein 1、AUF1、heterogeneous nuclear ribonucleoprotein D

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简介

Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Also binds to double- and single-stranded DNA sequences in a specific manner and functions a transcription factor. Each of the RNA-binding domains specifically can bind solely to a single-stranded non-monotonous 5'-UUAG-3' sequence and also weaker to the single-stranded 5'-TTAGGG-3' telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. Binding of RRM1 to DNA inhibits the formation of DNA quadruplex structure which may play a role in telomere elongation. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. May play a role in the regulation of the rhythmic expression of circadian clock core genes. Directly binds to the 3'UTR of CRY1 mRNA and induces CRY1 rhythmic translation. May also be involved in the regulation of PER2 translation.

关联

100 项与 HNRNPD 相关的临床结果

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100 项与 HNRNPD 相关的转化医学

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0 项与 HNRNPD 相关的专利（医药）

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449

项与 HNRNPD 相关的文献（医药）

2024-02-20·Molecular carcinogenesis

RhoGDIβ inhibition via miR-200c/AUF1/SOX2/miR-137 axis contributed to lncRNA MEG3 downregulation-mediated malignant transformation of human bronchial epithelial cells.

Article

作者: Yichao Yang ; Zhongxian Tian ; Lijiong He ; Hao Meng ; Xiaomin Xie ; Ziyi Yang ; Xinxing Wang ; Yunping Zhao ; Chuanshu Huang

Nickel pollution is a recognized factor contributing to lung cancer. Understanding the molecular mechanisms of its carcinogenic effects is crucial for lung cancer prevention and treatment. Our previous research identified the downregulation of a long noncoding RNA, maternally expressed gene 3 (MEG3), as a key factor in transforming human bronchial epithelial cells (HBECs) into malignant cells following nickel exposure. In our study, we found that deletion of MEG3 also reduced the expression of RhoGDIβ. Notably, artificially increasing RhoGDIβ levels counteracted the malignant transformation caused by MEG3 deletion in HBECs. This indicates that the reduction in RhoGDIβ contributes to the transformation of HBECs due to MEG3 deletion. Further exploration revealed that MEG3 downregulation led to enhanced c-Jun activity, which in turn promoted miR-200c transcription. High levels of miR-200c subsequently increased the translation of AUF1 protein, stabilizing SOX2 messenger RNA (mRNA). This stabilization affected the regulation of miR-137, SP-1 protein translation, and the suppression of RhoGDIβ mRNA transcription and protein expression, leading to cell transformation. Our study underscores the co-regulation of RhoGDIβ expression by long noncoding RNA MEG3, multiple microRNAs (miR-200c and miR-137), and RNA-regulated transcription factors (c-Jun, SOX2, and SP1). This intricate network of molecular events sheds light on the nature of lung tumorigenesis. These novel findings pave the way for developing targeted strategies for the prevention and treatment of human lung cancer based on the MEG3/RhoGDIβ pathway.

2024-02-16·Science advances

Enterovirus evolution reveals the mechanism of an RNA-targeted antiviral and determinants of viral replication.

Article

作者: Jesse Davila-Calderon ; Mei-Ling Li ; Srinivasa R Penumutchu ; Christina Haddad ; Linzy Malcolm ; Josephine King ; Amanda E Hargrove ; Gary Brewer ; Blanton S Tolbert

Selective pressures on viruses provide opportunities to establish target site specificity and mechanisms of antivirals. Enterovirus (EV)-A71 with resistant mutations in the stem loop (SL) II internal ribosome entry site (IRES) (SLII^resist) were selected at low doses of the antiviral dimethylamiloride (DMA)-135. The EV-A71 mutants were resistant to DMA-135 at concentrations that inhibit replication of wild-type virus. EV-A71 IRES structures harboring resistant mutations induced efficient expression of Luciferase messenger RNA in the presence of noncytotoxic doses of DMA-135. Nuclear magnetic resonance indicates that the mutations change the structure of SLII at the binding site of DMA-135 and at the surface recognized by the host protein AU-rich element/poly(U)-binding/degradation factor 1 (AUF1). Biophysical studies of complexes formed between AUF1, DMA-135, and either SLII or SLII^resist show that DMA-135 stabilizes a ternary complex with AUF1-SLII but not AUF1-SLII^resist. This work demonstrates how viral evolution elucidates the (DMA-135)-RNA binding site specificity in cells and provides insights into the viral pathways inhibited by the antiviral.

2024-02-05·International journal of biological macromolecules

Human RNA-binding protein HNRNPD interacts with and regulates the repair of deoxyribouridine in DNA.

Article

作者: Ziyu Wang ; Minghui Qu ; Sijia Chang ; Xiaoxia Dai ; Changjun You

Deoxyribouridine (dU) is an abnormal nucleoside in DNA and plays vital roles in multiple biological and physiological processes. Here, we conducted a mass spectrometry-based screen for dU-binding proteins and found that the heterogeneous nuclear ribonucleoprotein D (HNRNPD) could preferentially bind to dU-containing DNA. We also discovered that HNRNPD engages in the 5-Fluorouracil (5FU)-induced DNA damage response and can modulate the repair of dU in DNA in vitro and in human cells. Moreover, using a shuttle vector- and next-generation sequencing-based method, we unveiled the crucial role of HNRNPD in promoting the replicative bypass of dU in human cells. Taken together, these findings suggested that HNRNPD is a novel dU-bearing DNA-binding protein capable of regulating the removal of dU in DNA, and provided new insights into the molecular mechanisms of dU-associated diseases.

项与 HNRNPD 相关的新闻（医药）

2024-03-05

·今日头条

环状RNA新发现！复旦大学发文揭示癌症转移最新分子机制和预防靶点

环状RNA（circRNAs）是一类独特的共价闭合非编码RNA亚群，具有独特的结构特征、出色的稳定性、高保守性和丰富的表达。近日，复旦大学研究团队在期刊《Cancer Letters》上在线发表题为“CircUBE3A(2,3,4,5) promotes adenylate-uridylate-rich binding factor 1 nuclear translocation to suppress prostate cancer metastasis”的研究论文，本研究将circUBE3A（2,3,4,5）表征为一种功能性circRNA，并将其作为预防前列腺癌转移的极具前景的靶点。前列腺癌（PCa）是男性中主要的恶性肿瘤，其每年的发病率持续上升，2023年占据全球男性癌症新发病例的29%。手术干预和放射治疗仍然是局部PCa的有效治疗方式。然而，在转移性前列腺癌治疗中，迫切需要改进的治疗方案。因此，探索调控PCa转移的分子机制并开发有效干预措施至关重要。环状RNA（circRNAs）是一类独特的共价闭合非编码RNA亚群，具有独特的结构特征、出色的稳定性、高保守性和丰富的表达。已经确定，侧翼内含子互补序列是导致circRNA形成的反向剪接的重要贡献者。在功能上，circRNAs可以通过作为蛋白质复合物的支架或与RNA结合蛋白（RBPs）相互作用来调节基因表达，影响基因的表达，包括它们的亲本基因。它们还可以作为microRNAs（miRNAs）的分子海绵，并展示出编码肽的能力，例如circCCDC7（15,16,17,18,19）和circ-FBXW7。越来越多证据表明，circRNAs在调控各种癌症中发挥着关键作用，使它们有望成为临床生物标志物和可行的治疗干预靶点。这项研究利用体外筛选细胞模型和高通量circRNA测序系统，鉴定了一个与前列腺癌（PCa）相关的circRNA（circBase ID: hsa_circ_0000586）。由于它来源于泛素蛋白连接酶E3A（UBE3A）基因的四个外显子（外显子2、3、4和5），研究人员按照最新的命名指南将其命名为circUBE3A（2,3,4,5）。发现circUBE3A（2,3,4,5）在PCa组织中下调，并与肿瘤恶性相关。它通过与AUF1相互作用并促进其向细胞核的易位来抑制PCa的转移。因此，AUF1在细胞质中的缺乏导致MTHFD2 mRNA稳定性降低，导致波形蛋白表达下调。两对短倒置重复序列（TSIR）被鉴定为协同增强 circUBE3A（2,3,4,5）的形成。研究发现揭示了circRNA在转移中新的调控作用，并确定了治疗PCa转移的新分子机制。综上所述，本研究将circUBE3A（2,3,4,5）表征为一种功能性circRNA，并将其作为预防前列腺癌转移的极具前景的靶点。参考资料：https://www.sciencedirect.com/science/article/pii/S0304383524001368 内容来源于网络，如有侵权，请联系删除。

放射疗法信使RNA

2023-05-02

·PRNewswire

REGENXBIO Announces Presentations at the American Society of Gene & Cell Therapy 26th Annual Meeting

ROCKVILLE, Md., May 2, 2023 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced presentations at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting, taking place in Los Angeles, California from May 16 through 20, 2023. The presentations highlight the Company's end-to-end capabilities across clinical development and research and early development. The presentations will be presented as follows: Oral Presentations: Abstract Title: AUF1 Gene Therapy for Duchenne Muscular Dystrophy Increases Durable Endogenous Utrophin Expression, Muscle Regeneration and Muscle Function Performance in Pre-clinical Animal Studies (abstract #135) Presenter: Dounia Abbadi, Postdoctoral Fellow, NYU Langone Medical Center Session: Gene Tx Approaches for Muscle & Skeletal Diseases Date/Time: Thursday, May 18, 2023, 2:38-2:55 p.m. PST Abstract Title: Mechanistic Evaluation of Liver-specific Transgene Repression from AAV Vectors in Non-Human Primates and Minipigs (abstract #249) Presenter: Zhuo Wang, Ph.D., Scientist II, Research & Early Development at REGENXBIO Session: AAV Vector Genome Biology & Engineering II Date/Time: Friday, May 19 3:45-4:00 p.m. PST Poster Presentations: Abstract Title: RGX-121 gene therapy for the treatment of neuronopathic mucopolysaccharidosis type II (MPS II): Interim analysis of data from the first in human study (abstract #807) Presenter: Paul Harmatz, M.D., Professor in Residence at University of California, San Francisco Session: Wednesday Poster Session Date/Time: Wednesday, May 17, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: In Silico Prediction and In Vivo Testing of Promoters Targeting GABAergic Inhibitory Neurons (abstract #385) Presenter: Robert Duba-Kiss, Ph.D. Candidate, Pharmacology/Neuroscience at University of Toronto University of Toronto Session: Wednesday Poster Session Date/Time: Wednesday, May 17, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: Development of AAV-Expressed C5 Inhibitor to Locally Suppress Complement Pathway Activation in the Eye as a Potential Treatment for Dry Age-related Macular Degeneration (abstract #364) Presenter: Wei-Hua Lee, Ph.D., Senior Scientist, Research & Early Development at REGENXBIO Session: Wednesday Poster Session Date/Time: Wednesday, May 17, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: Addition of a Protein Domain from the Dystrophin C-Terminus Improves Functional and Biochemical Properties of AAV-Encoded Microdystrophin (abstract #668) Presenter: Steven Foltz, Ph.D., Senior Scientist, Research & Early Development at REGENXBIO Session: Wednesday Poster Session Date/Time: Wednesday, May 17, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: Optimization of AAV-DARPin Fusions to Redirect Capsid Tropism (abstract #447) Presenter: Elad Firnberg, Ph.D., Senior Scientist, Research & Early Development at REGENXBIO Session: Wednesday Poster Session Date/Time: Wednesday, May 17, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: RGX-111 gene therapy for the treatment of severe mucopolysaccharidosis type I (MPS I): Interim analysis of data from the first in human study (abstract #932) Presenter: Laura Pisani-Betancourt, MD, MBA, FACMG, Senior Medical Director, Clinical Development Lead at REGENXBIO Session: Thursday Poster Session Date/Time: Thursday May 18, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: Local Delivery of Vectorized Therapeutics Targeting a Pro-inflammatory Cytokine Effectively Reduces Disease Severity in a Mouse Model of Non-Infectious Uveitis (abstract #860) Presenter: Jessica Gumerson, Ph.D., Scientist II, Research & Early Development at REGENXBIO Session: Thursday Poster Session Date/Time: Thursday May 18, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: High Resolution Biodistribution Analysis Following Suprachoroidal Administration of a Pool of AAV3B, AAV8, and AAV9 Vectors to Non-Human Primates Reveals Spatial and Cell-Based Tropism Differences (abstract #876) Presenter: April R. Giles, Ph.D., Senior Scientist, Research & Early Development at REGENXBIO Session: Thursday Poster Session Date/Time: Thursday, May 18, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: Utility of Cryofluorescence Tomography (CFT) as an Unbiased Method to Describe AAV Biodistribution (abstract #1278) Presenter: Samantha A. Yost, Ph.D., Senior Scientist, Research & Early Development at REGENXBIO Session: Friday Poster Session Date/Time: Friday, May 19, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: Development of a Self-Complementary AAV.U7snRNA Vector for Efficient Dystrophin Exon 53 Skipping (abstract #1565) Presenter: Randolph Qian, Ph.D., Scientist II, Research & Early Development at REGENXBIO Session: Friday Poster Session Date/Time: Friday, May 19, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST Abstract Title: Kinetic Analyses Reveal Very Early CpG-specific Antagonism to AAV-Mediated Transgene Expression: Implications for TLR9 Stimulatory Effects Prior to Effector T Cell Activation Following Gene Transfer (abstract #1487) Presenter: Justin D. Glenn, Ph.D., Senior Scientist, Research & Early Development at REGENXBIO Session: Friday Poster Session Date/Time: Friday, May 19, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST NAV® Technology Licensees: Abstract Title: AAV Vector DNA Carrying Two Concatenated miRNA Stem-Loops is Highly Homogenous and Stable in GLP-Grade AAV Product Presenter: Chenxia HE, Ph.D., Director of Gene Therapy at uniQure, in collaboration with REGENXBIO Session: AAV Vectors – Product Development Manufacturing: Analytics & Stability Studies Date/Time: Thursday, May 18, 2023, 1:45-2:00 p.m. PST Abstract Title: Preclinical Proof-of-Concept of AMT-260, a Novel AAV9-Dual microRNA-Based Vector Targeting GRIK2 for the Treatment of Temporal Lobe Epilepsy (abstract #1159) Presenter: Nick Pearson, Head of Toxicology & Translational Safety at uniQure, in collaboration with REGENXBIO Session: Thursday Poster Session Date/Time: Thursday, May 18, 2023 12:00-2:00 p.m. PST & 5:30-7:00 p.m. PST About REGENXBIO Inc. REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO's NAV Technology Platform, a proprietary adeno-associated virus (AAV) gene delivery platform, consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8 and AAV9. REGENXBIO and its third-party NAV Technology Platform Licensees are applying the NAV Technology Platform in the development of a broad pipeline of candidates, including late-stage and commercial programs, in multiple therapeutic areas. REGENXBIO is committed to a "5x'25" strategy to progress five AAV Therapeutics from our internal pipeline and licensed programs into pivotal-stage or commercial products by 2025. Contacts: Dana Cormack Corporate Communications [email protected] Investors: Chris Brinzey ICR Westwicke 339-970-2843 [email protected] SOURCE REGENXBIO Inc.

基因疗法临床研究