keyword
https://read.qxmd.com/read/37131644/decoding-complexity-in-biomolecular-recognition-of-dna-i-motifs
#21
Kamyar Yazdani, Srinath Seshadri, Desiree Tillo, Charles Vinson, John S Schneekloth
DNA i-motifs (iMs) are non-canonical C-rich secondary structures implicated in numerous cellular processes. Though iMs exist throughout the genome, our understanding of iM recognition by proteins or small molecules is limited to a few examples. We designed a DNA microarray containing 10,976 genomic iM sequences to examine the binding profiles of four iM-binding proteins, mitoxantrone, and the iMab antibody. iMab microarray screens demonstrated that pH 6.5, 5% BSA buffer was optimal, and fluorescence was correlated with iM C-tract length...
April 21, 2023: bioRxiv
https://read.qxmd.com/read/37095740/serum-glucose-starvation-strikingly-reduce-heterogeneous-nuclear-ribonucleoprotein-a1-protein-and-its-target-cyclin-d1
#22
JOURNAL ARTICLE
Tetsuyuki Takahashi, Yuri Ando, Hirona Ichikawa, Koichi Tsuneyama, Takao Hijikata
Our investigation to explore cellular alterations related to undernutrition in cancer cells revealed that the protein level of heterogenous nuclear ribonucleoprotein A1 (hnRNP A1) is drastically decreased by serum/glucose starvation. Its loss was reversible, serum/glucose starvation-specific, and universal throughout cell types and species. The hnRNP A1 mRNA level and hnRNP A1 mRNA/protein stability were not altered under this condition. CCND1 mRNA, which we newly identified as the binding target of hnRNP A1, was decreased by serum/glucose starvation...
April 24, 2023: FEBS Journal
https://read.qxmd.com/read/37061119/m-6-a-modification-of-cyclin-d1-and-c-myc-iress-in-glioblastoma-controls-itaf-activity-and-resistance-to-mtor-inhibition
#23
JOURNAL ARTICLE
Angelica Benavides-Serrato, Jacquelyn T Saunders, Sunil Kumar, Brent Holmes, Kennedy E Benavides, Muhammad T Bashir, Robert N Nishimura, Joseph Gera
A major mechanism conferring resistance to mTOR inhibitors is activation of a salvage pathway stimulating internal ribosome entry site (IRES)-mediated mRNA translation, driving the synthesis of proteins promoting resistance of glioblastoma (GBM). Previously, we found this pathway is stimulated by the requisite IRES-trans-acting factor (ITAF) hnRNP A1, which itself is subject to phosphorylation and methylation events regulating cyclin D1 and c-myc IRES activity. Here we describe the requirement for m6 A-modification of IRES RNAs for efficient translation and resistance to mTOR inhibition...
April 13, 2023: Cancer Letters
https://read.qxmd.com/read/36997512/the-rna-binding-protein-hnrnp-f-is-required-for-the-germinal-center-b-cell-response
#24
JOURNAL ARTICLE
Hengjun Huang, Yuxing Li, Gaopu Zhang, Gui-Xin Ruan, Zhijian Zhu, Wenjing Chen, Jia Zou, Rui Zhang, Jing Wang, Yu Ouyang, Shengli Xu, Xijun Ou
The T cell-dependent (TD) antibody response involves the generation of high affinity, immunoglobulin heavy chain class-switched antibodies that are generated through germinal center (GC) response. This process is controlled by coordinated transcriptional and post-transcriptional gene regulatory mechanisms. RNA-binding proteins (RBPs) have emerged as critical players in post-transcriptional gene regulation. Here we demonstrate that B cell-specific deletion of RBP hnRNP F leads to diminished production of class-switched antibodies with high affinities in response to a TD antigen challenge...
March 30, 2023: Nature Communications
https://read.qxmd.com/read/36982587/intracellular-conformation-of-amyotrophic-lateral-sclerosis-causative-tdp-43
#25
JOURNAL ARTICLE
Akira Kitamura, Sachiko Yuno, Rintaro Kawamura, Masataka Kinjo
Transactive response element DNA/RNA-binding protein 43 kDa (TDP-43) is the causative protein of amyotrophic lateral sclerosis (ALS); several ALS-associated mutants of TDP-43 have been identified. TDP-43 has several domains: an N-terminal domain, two RNA/DNA-recognition motifs, and a C-terminal intrinsically disordered region (IDR). Its structures have been partially determined, but the whole structure remains elusive. In this study, we investigate the possible end-to-end distance between the N- and C-termini of TDP-43, its alterations due to ALS-associated mutations in the IDR, and its apparent molecular shape in live cells using Förster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS)...
March 14, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36930682/tdp-43-and-other-hnrnps-regulate-cryptic-exon-inclusion-of-a-key-als-ftd-risk-gene-unc13a
#26
JOURNAL ARTICLE
Yuka Koike, Sarah Pickles, Virginia Estades Ayuso, Karen Jansen-West, Yue A Qi, Ziyi Li, Lillian M Daughrity, Mei Yue, Yong-Jie Zhang, Casey N Cook, Dennis W Dickson, Michael Ward, Leonard Petrucelli, Mercedes Prudencio
A major function of TAR DNA-binding protein-43 (TDP-43) is to repress the inclusion of cryptic exons during RNA splicing. One of these cryptic exons is in UNC13A, a genetic risk factor for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The accumulation of cryptic UNC13A in disease is heightened by the presence of a risk haplotype located within the cryptic exon itself. Here, we revealed that TDP-43 extreme N-terminus is important to repress UNC13A cryptic exon inclusion. Further, we found hnRNP L, hnRNP A1, and hnRNP A2B1 bind UNC13A RNA and repress cryptic exon inclusion, independently of TDP-43...
March 17, 2023: PLoS Biology
https://read.qxmd.com/read/36921676/%C3%AE-hydroxybutyrate-alleviates-cartilage-senescence-through-hnrnp-a1-mediated-up-regulation-of-pten
#27
JOURNAL ARTICLE
Guang Xia, Zi Wen, Lina Zhang, Junjie Huang, Xinxing Wang, Chi Liang, Xiaoyu Cui, Xu Cao, Song Wu
Senescence chondrocytes play an important role in Osteoarthritis (OA) progression. However, alleviating OA progression through senescent chondrocyte intervention still faces great challenges. β-Hydroxybutyrate (BHB) exhibits anti-senescence effects in a variety of age-related dis-eases, but its role in osteoarthritis remains poorly understood. To explore the molecular mechanisms, gene sequencing was used to identify critical genes and potential cellular signaling pathways and male SD rats were used to generate an osteoarthritis model...
March 13, 2023: Experimental Gerontology
https://read.qxmd.com/read/36755337/retraction-note-hnrnp-a1-mediated-alternative-splicing-of-ccdc50-contributes-to-cancer-progression-of-clear-cell-renal-cell-carcinoma-via-znf395
#28
Guoliang Sun, Hui Zhou, Ke Chen, Jin Zeng, Yangjun Zhang, Libin Yan, Weimin Yao, Junhui Hu, Tao Wang, Jinchun Xing, Kefeng Xiao, Lily Wu, Zhangqun Ye, Hua Xu
No abstract text is available yet for this article.
February 8, 2023: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/36560896/structure-and-function-analysis-of-sam68-and-hnrnp-a1-synergy-in-the-exclusion-of-exon-7-from-smn2-transcripts
#29
JOURNAL ARTICLE
Marta Nadal, Rosa Anton, Jonatan Dorca-Arévalo, Eva Estébanez-Perpiñá, Eduardo F Tizzano, Pablo Fuentes-Prior
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the absence of a functional copy of the Survival of Motor Neuron 1 gene (SMN1). The nearly identical paralog, SMN2, cannot compensate for the loss of SMN1 because exon 7 is aberrantly skipped from most SMN2 transcripts, a process mediated by synergistic activities of Sam68/KHDRBS1 and hnRNP A1. This results in the production of a truncated, non-functional protein that is rapidly degraded. Here we present several crystal structures of Sam68 RNA-binding domain (RBD)...
December 22, 2022: Protein Science
https://read.qxmd.com/read/36460805/a-comprehensive-understanding-of-hnrnp-a1-role-in-cancer-new-perspectives-on-binding-with-noncoding-rna
#30
REVIEW
Luisa Siculella, Laura Giannotti, Benedetta Di Chiara Stanca, Francesco Spedicato, Matteo Calcagnile, Stefano Quarta, Marika Massaro, Fabrizio Damiano
The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is the most abundant and ubiquitously expressed member of the heterogeneous nuclear ribonucleoproteins family (hnRNPs). hnRNP A1 is an RNA-binding protein associated with complexes active in diverse biological processes such as RNA splicing, transactivation of gene expression, and modulation of protein translation. It is overexpressed in several cancers, where it actively promotes the expression and translation of several key proteins and regulators associated with tumorigenesis and cancer progression...
December 2, 2022: Cancer Gene Therapy
https://read.qxmd.com/read/36382566/hnrnp-a1-dysfunction-in-oligodendrocytes-contributes-to-the-pathogenesis-of-multiple-sclerosis
#31
JOURNAL ARTICLE
Ali Jahanbazi Jahan-Abad, Hannah E Salapa, Cole D Libner, Patricia A Thibault, Michael C Levin
Oligodendrocyte (OL) damage and death are prominent features of multiple sclerosis (MS) pathology, yet mechanisms contributing to OL loss are incompletely understood. Dysfunctional RNA binding proteins (RBPs), hallmarked by nucleocytoplasmic mislocalization and altered expression, have been shown to result in cell loss in neurologic diseases, including in MS. Since we previously observed that the RBP heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was dysfunctional in neurons in MS, we hypothesized that it might also contribute to OL pathology in MS and relevant models...
November 16, 2022: Glia
https://read.qxmd.com/read/36339596/hnrnp-a1-in-rna-metabolism-regulation-and-as-a-potential-therapeutic-target
#32
REVIEW
Jianguo Feng, Jianlong Zhou, Yunxiao Lin, Wenhua Huang
Abnormal RNA metabolism, regulated by various RNA binding proteins, can have functional consequences for multiple diseases. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an important RNA binding protein, that regulates various RNA metabolic processes, including transcription, alternative splicing of pre-mRNA, translation, miRNA processing and mRNA stability. As a potent splicing factor, hnRNP A1 can regulate multiple splicing events, including itself, collaborating with other cooperative or antagonistical splicing factors by binding to splicing sites and regulatory elements in exons or introns...
2022: Frontiers in Pharmacology
https://read.qxmd.com/read/36322053/optimization-of-ripca-for-the-live-cell-detection-of-pre-microrna-protein-interactions
#33
JOURNAL ARTICLE
Sydney Rosenblum, Amanda Lee Garner
<p class="Abstract" style="margin: 0in 0in 30pt; text-align: justify; line-height: 11.25pt; font-size: 8pt; font-family: Arial, sans-serif; caret-color: rgb(0, 0, 0); color: rgb(0, 0, 0);">Advancements in methods for identifying RNA-protein interactions (RPIs) on a large scale has necessitated the development of assays for validation of these interactions, particularly in living cells. We previously reported the development of RiPCA (RNA interaction with Protein-mediated Complementation Assay) to enable the cellular detection of the well-characterized interaction between the pre-microRNA, pre-let-7, and its RNA-binding protein (RBP) partner Lin28...
November 2, 2022: Chembiochem: a European Journal of Chemical Biology
https://read.qxmd.com/read/36314424/clinical-heterogeneity-in-a-family-with-flail-arm-syndrome-and-review-of-hnrnpa1-related-spectrum
#34
JOURNAL ARTICLE
Xiaochen Han, Feixia Zhan, Yuxin Yao, Li Cao, Jianguo Liu, Sheng Yao
OBJECTIVE: Flail arm syndrome (FAS) is one of the atypical subtypes of amyotrophic lateral sclerosis (ALS). Mutations in hnRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare genetic cause of ALS. Herein, marked clinical heterogeneity of FAS in a pedigree with a known hnRNPA1 variant was described to raise early awareness of the ALS variant. Furtherly, a literature review of the hnRNPA1-related spectrum was made to summarize the clinical and genetic characteristics...
October 31, 2022: Annals of Clinical and Translational Neurology
https://read.qxmd.com/read/36255739/a-splicing-silencer-in-smn2-intron-6-is-critical-in-spinal-muscular-atrophy
#35
JOURNAL ARTICLE
Li Wang, Yinfeng Ji, Yuqing Chen, Jialin Bai, Peng Gao, Pengchao Feng
Spinal muscular atrophy (SMA) is a fatal neuromuscular disease caused by homozygous deletions or mutations of the SMN1 gene. SMN2 is a paralogous gene of SMN1 and a modifying gene of SMA. A better understanding of how SMN2 exon 7 splicing is regulated helps discover new therapeutic targets for SMA therapy. Based on an antisense walk method to map exonic and intronic splicing silencers (ESSs and ISSs) in SMN2 exon 7 and the proximal regions of its flanking introns, we identified one ISS (ISS6-KH) at upstream of the branch point site in intron 6...
October 18, 2022: Human Molecular Genetics
https://read.qxmd.com/read/36220570/aerocyte-specification-and-lung-adaptation-to-breathing-is-dependent-on-alternative-splicing-changes
#36
JOURNAL ARTICLE
Marta F Fidalgo, Catarina G Fonseca, Paulo Caldas, Alexandre Asf Raposo, Tania Balboni, Lenka Henao-Mišíková, Ana R Grosso, Francisca F Vasconcelos, Cláudio A Franco
Adaptation to breathing is a critical step in lung function and it is crucial for organismal survival. Alveoli are the lung gas exchange units and their development, from late embryonic to early postnatal stages, requires feedbacks between multiple cell types. However, how the crosstalk between the alveolar cell types is modulated to anticipate lung adaptation to breathing is still unclear. Here, we uncovered a synchronous alternative splicing switch in multiple genes in the developing mouse lungs at the transition to birth, and we identified hnRNP A1, Cpeb4, and Elavl2/HuB as putative splicing regulators of this transition...
December 2022: Life Science Alliance
https://read.qxmd.com/read/36208849/position-dependent-effects-of-hnrnp-a1-a2-in-smn1-2-exon7-splicing
#37
JOURNAL ARTICLE
Jiaying Qiu, Ruobing Qu, Mengsi Lin, Jian Xu, Qingwen Zhu, Zhenyu Zhang, Junjie Sun
Heterogeneous nuclear ribonucleoprotein A1 and A2 (hnRNP A1/2) is a ubiquitously expressed RNA binding protein known to bind intronic or exonic splicing silencer. Binding of hnRNP A1/2 to survival of motor neuron gene (SMN1/2) exon 7 and flanking sequences strongly inhibits the inclusion of exon 7, which causes spinal muscular atrophy, a common genetic disorder. However, the role of hnRNP A1/2 on the side away from exon 7 is unclear. Here using antisense oligonucleotides, we fished an intronic splicing enhancer (ISE) near the 3'-splice site (SS) of intron 7 of SMN1/2...
October 5, 2022: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms
https://read.qxmd.com/read/36142139/tumor-promoting-actions-of-hnrnp-a1-in-hcc-are-associated-with-cell-cycle-mitochondrial-dynamics-and-necroptosis
#38
JOURNAL ARTICLE
Biao Zhao, Xiaochen Lv, Xiaoqi Zhao, Subinuer Maimaitiaili, Yuheng Zhang, Ke Su, Hang Yu, Cheng Liu, Tong Qiao
Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world. Although increasing evidence supports the role of heterogeneous ribonucleoprotein particle A1 (HNRNP A1) in tumor progression, the function of HNRNP A1 in HCC remains unclear. Here, we focused on the role of HNRNP A1 in the development of HCC. In this study, we found HNRNP A1 participates in many aspects of HCC, such as progression and prognosis. Our results showed that HNRNP A1 is upregulated in human HCC tissues and cell lines...
September 6, 2022: International Journal of Molecular Sciences
https://read.qxmd.com/read/36080449/optimization-of-bifunctional-antisense-oligonucleotides-for-regulation-of-mutually-exclusive-alternative-splicing-of-pkm-gene
#39
JOURNAL ARTICLE
Natalia Bartyś, Anna Pasternak, Jolanta Lisowiec-Wąchnicka
Oligonucleotide tools, as modulators of alternative splicing, have been extensively studied, giving a rise to new therapeutic approaches. In this article, we report detailed research on the optimization of bifunctional antisense oligonucleotides (BASOs), which are targeted towards interactions with hnRNP A1 protein. We performed a binding screening assay, Kd determination, and UV melting experiments to select sequences that can be used as a high potency binding platform for hnRNP A1. Newly designed BASOs were applied to regulate the mutually exclusive alternative splicing of the PKM gene...
September 3, 2022: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/35963429/ampk-related-protein-kinase-ark5-regulates-subcellular-localization-of-rna-binding-protein-hnrnp-a1-during-hypertonic-stress
#40
JOURNAL ARTICLE
Krishna Bhattarai, Travis Richard, Thet Fatica, Brianna Frangione, William G Willmore, Martin Holcik
The heterogeneous nuclear ribonucleoprotein hnRNP A1 is a nucleocytoplasmic-shuttling RNA-binding protein that plays an important role in nucleic acid metabolism and gene expression regulation. The function of hnRNP A1 is determined in part by its specific location within the cell. Although some work has been done to elucidate the signaling pathways that regulate the cellular localization of hnRNP A1, the precise mechanism(s), including physiological and pathophysiological conditions that alter hnRNP A1 localization, are not known...
August 10, 2022: Journal of Biological Chemistry
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