keyword
https://read.qxmd.com/read/37787459/proximity-proteomics-revealed-aberrant-mrna-splicing-elicited-by-als-linked-profilin-1-mutants
#21
JOURNAL ARTICLE
Songbo Wei, YenYu Yang, Yinsheng Wang
Profilin 1 (PFN1) is a cytoskeleton protein that modulates actin dynamics through binding to monomeric actin and polyproline-containing proteins. Mutations in PFN1 have been linked to the pathogenesis of familial amyotrophic lateral sclerosis (ALS). Here, we employed an unbiased proximity labeling strategy in combination with proteomic analysis for proteome-wide profiling of proteins that differentially interact with mutant and wild-type (WT) PFN1 proteins in human cells. We uncovered 11 mRNA splicing proteins that are preferentially enriched in the proximity proteomes of the two ALS-linked PFN1 variants, C71G and M114T, over that of wild-type PFN1...
October 17, 2023: Analytical Chemistry
https://read.qxmd.com/read/37741908/captes-enables-locus-specific-dissection-of-transcriptional-outputs-from-reference-and-nonreference-transposable-elements
#22
JOURNAL ARTICLE
Xuemei Li, Keying Lu, Xiao Chen, Kailing Tu, Dan Xie
Transposable elements (TEs) serve as both insertional mutagens and regulatory elements in cells, and their aberrant activity is increasingly being revealed to contribute to diseases and cancers. However, measuring the transcriptional consequences of nonreference and young TEs at individual loci remains challenging with current methods, primarily due to technical limitations, including short read lengths generated and insufficient coverage in target regions. Here, we introduce a long-read targeted RNA sequencing method, Cas9-assisted profiling TE expression sequencing (capTEs), for quantitative analysis of transcriptional outputs for individual TEs, including transcribed nonreference insertions, noncanonical transcripts from various transcription patterns and their correlations with expression changes in related genes...
September 23, 2023: Communications Biology
https://read.qxmd.com/read/37738962/alu-transposable-elements-rewire-enhancer-promoter-network-through-rna-pairing
#23
JOURNAL ARTICLE
Xingzhao Wen, Sheng Zhong
A recent study by Liang et al.1 reveals that interacting enhancer RNAs (eRNAs) and promoter-transcribed upstream antisense RNAs (uaRNAs) can identify enhancer-promoter interactions. Complementary sequences within the interacting eRNAs and uaRNAs, predominantly Alu sequences, confer the specificity for eRNA-uaRNA pairing and hence enhancer-promoter recognition.
September 21, 2023: Molecular Cell
https://read.qxmd.com/read/37691856/nanoparticle-delivery-of-immunostimulatory-alu-rna-for-cancer-immunotherapy
#24
JOURNAL ARTICLE
Kyle M Garland, Alexander J Kwiatkowski, John T Tossberg, Philip S Crooke, Thomas M Aune, John T Wilson
UNLABELLED: It was recently found that patients with relapsing remitting multiple sclerosis exhibit widespread loss of adenosine-to-inosine (A-to-I) RNA editing, which contributes to the accumulation of immunostimulatory double-stranded Alu RNA in circulating leukocytes and an attendant increase in levels of proinflammatory cytokines (e.g., type I IFNs). A specific Alu RNA (i.e., AluJb RNA) was implicated in activating multiple RNA-sensing pathways and found to be a potent innate immune agonist...
September 2023: Cancer Res Commun
https://read.qxmd.com/read/37652985/profiling-of-repetitive-rna-sequences-in-the-blood-plasma-of-patients-with-cancer
#25
JOURNAL ARTICLE
Roman E Reggiardo, Sreelakshmi Velandi Maroli, Vikas Peddu, Andrew E Davidson, Alexander Hill, Erin LaMontagne, Yassmin Al Aaraj, Miten Jain, Stephen Y Chan, Daniel H Kim
Liquid biopsies provide a means for the profiling of cell-free RNAs secreted by cells throughout the body. Although well-annotated coding and non-coding transcripts in blood are readily detectable and can serve as biomarkers of disease, the overall diagnostic utility of the cell-free transcriptome remains unclear. Here we show that RNAs derived from transposable elements and other repeat elements are enriched in the cell-free transcriptome of patients with cancer, and that they serve as signatures for the accurate classification of the disease...
August 31, 2023: Nature Biomedical Engineering
https://read.qxmd.com/read/37635251/a-comparative-study-of-in-vitro-air-liquid-interface-culture-models-of-the-human-airway-epithelium-evaluating-cellular-heterogeneity-and-gene-expression-at-single-cell-resolution
#26
JOURNAL ARTICLE
Rachel A Prescott, Alec P Pankow, Maren de Vries, Keaton M Crosse, Roosheel S Patel, Mark Alu, Cynthia Loomis, Victor Torres, Sergei Koralov, Ellie Ivanova, Meike Dittmann, Brad R Rosenberg
BACKGROUND: The airway epithelium is composed of diverse cell types with specialized functions that mediate homeostasis and protect against respiratory pathogens. Human airway epithelial (HAE) cultures at air-liquid interface are a physiologically relevant in vitro model of this heterogeneous tissue and have enabled numerous studies of airway disease. HAE cultures are classically derived from primary epithelial cells, the relatively limited passage capacity of which can limit experimental methods and study designs...
August 28, 2023: Respiratory Research
https://read.qxmd.com/read/37604334/sine-vntr-alu%C3%A2-retrotransposon%C3%A2-insertion-as-a%C3%A2-novel-mutational-event-underlying-glanzmann-thrombasthenia
#27
JOURNAL ARTICLE
Jiasheng Zhang, Jie Tang, Guoqiang Li, Niu Li, Jian Wang, Ruen Yao, Tingting Yu
BACKGROUND: Glanzmann thrombasthenia (GT) is an autosomal recessive platelet aggregation disorder caused by mutations in ITGA2B or ITGB3. OBJECTIVES: We aim to assess the phenotype and investigate the genetic etiology of a GT pedigree. METHODS: A patient with bleeding manifestations and mild mental retardation was enrolled. Complete blood count, coagulation, and platelet aggregation tests were performed. Causal mutations were identified via whole exome and genome sequencing, and subsequently confirmed through polymerase chain reaction (PCR) and Sanger sequencing...
August 19, 2023: Journal of Thrombosis and Haemostasis: JTH
https://read.qxmd.com/read/37604131/sars-cov-2-infection-severity-and-mortality-is-modulated-by-repeat-mediated-regulation-of-alternative-splicing
#28
JOURNAL ARTICLE
Priyanka Mehta, Partha Chattopadhyay, Varsha Ravi, Bansidhar Tarai, Sandeep Budhiraja, Rajesh Pandey
Like single-stranded RNA viruses, SARS-CoV-2 hijacks the host transcriptional machinery for its own replication. Numerous traditional differential gene expression-based investigations have examined the diverse clinical symptoms caused by SARS-CoV-2 infection. The virus, on the other hand, also affects the host splicing machinery, causing host transcriptional dysregulation, which can lead to diverse clinical outcomes. Hence, in this study, we performed host transcriptome sequencing of 125 hospital-admitted COVID-19 patients to understand the transcriptomic differences between the severity sub-phenotypes of mild, moderate, severe, and mortality...
August 21, 2023: Microbiology Spectrum
https://read.qxmd.com/read/37580774/efficiency-of-mitochondrial-genes-and-nuclear-alu-elements-in-detecting-human-dna-in-blood-meals-of-anopheles-stephensi-mosquitoes-a-time-course-study
#29
JOURNAL ARTICLE
Fahimeh Talebzadeh, Masoud Ghadipasha, Jaber Gharehdaghi, Reza Raoofian, Kamal Azam, Mona Koosha, Mohammad Ali Oshaghi
BACKGROUND: The time required for PCR detection of DNA in human blood meals in vector mosquitoes may vary, depending on the molecular markers used, based on the size and copy number of the amplicons. Detailed knowledge of the blood-feeding behavior of mosquito populations in nature is an essential component for evaluating their vectorial capacity and for assessing the roles of individual vertebrates as potential hosts involved in the transmission of vector-borne diseases. METHODS: Laboratory experiments were conducted to compare the time course of PCR detection of DNA in human blood meals from individual blood-fed Anopheles stephensi mosquitoes, using loci with different characteristics, including two mitochondrial DNA (mtDNA) genes, cytB (228 bp) and 16S ribosomal RNA (rRNA) (157 bp) and nuclear Alu-repeat elements (226 bp) at different time points after the blood meal...
August 14, 2023: Parasites & Vectors
https://read.qxmd.com/read/37476414/integrative-profiling-of-extrachromosomal-circular-dna-in-placenta-and-maternal-plasma-provides-insights-into-the-biology-of-fetal-growth-restriction-and-reveals-potential-biomarkers
#30
JOURNAL ARTICLE
Minhuan Lin, Yiqing Chen, Shuting Xia, Zhiming He, Xuegao Yu, Linhuan Huang, Shaobin Lin, Binrun Liang, Ziliang Huang, Shiqiang Mei, Dong Liu, Lingling Zheng, Yanmin Luo
Introduction: Fetal growth restriction (FGR) is a placenta-mediated pregnancy complication that predisposes fetuses to perinatal complications. Maternal plasma cell-free DNA harbors DNA originating from placental trophoblasts, which is promising for the prenatal diagnosis and prediction of pregnancy complications. Extrachromosomal circular DNA (eccDNA) is emerging as an ideal biomarker and target for several diseases. Methods: We utilized eccDNA sequencing and bioinformatic pipeline to investigate the characteristics and associations of eccDNA in placenta and maternal plasma, the role of placental eccDNA in the pathogenesis of FGR, and potential plasma eccDNA biomarkers of FGR...
2023: Frontiers in Genetics
https://read.qxmd.com/read/37470992/transcriptome-wide-profiling-of-a-to-i-rna-editing-by-slic-seq
#31
JOURNAL ARTICLE
Qi Wei, Shaoqing Han, Kexin Yuan, Zhiyong He, Yuqi Chen, Xin Xi, Jingyu Han, Shen Yan, Yingying Chen, Bifeng Yuan, Xiaocheng Weng, Xiang Zhou
Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional processing event involved in diversifying the transcriptome and is responsible for various biological processes. In this context, we developed a new method based on the highly selective cleavage activity of Endonuclease V against Inosine and the universal activity of sodium periodate against all RNAs to enrich the inosine-containing RNA and accurately identify the editing sites. We validated the reliability of our method in human brain in both Alu and non-Alu elements...
July 20, 2023: Nucleic Acids Research
https://read.qxmd.com/read/37438529/complementary-alu-sequences-mediate-enhancer-promoter-selectivity
#32
JOURNAL ARTICLE
Liang Liang, Changchang Cao, Lei Ji, Zhaokui Cai, Di Wang, Rong Ye, Juan Chen, Xiaohua Yu, Jie Zhou, Zhibo Bai, Ruoyan Wang, Xianguang Yang, Ping Zhu, Yuanchao Xue
Enhancers determine spatiotemporal gene expression programs by engaging with long-range promoters1-4 . However, it remains unknown how enhancers find their cognate promoters. We recently developed a RNA in situ conformation sequencing technology to identify enhancer-promoter connectivity using pairwise interacting enhancer RNAs and promoter-derived noncoding RNAs5,6 . Here we apply this technology to generate high-confidence enhancer-promoter RNA interaction maps in six additional cell lines. Using these maps, we discover that 37...
July 12, 2023: Nature
https://read.qxmd.com/read/37417275/expression-of-alu-repeat-in-blood-plasma-of-patients-with-breast-cancer-during-neoadjuvant-chemotherapy-an-exploratory-study
#33
JOURNAL ARTICLE
E Özgür, F Ferhatoglu, F Sen, P Saip, U Gezer
BACKGROUND: Locally advanced breast cancer (LABC) rates are unusually high in developing countries. There is a need for the identification of predictive biomarkers for the selection of patients who could benefit from neoadjuvant chemotherapy (NAC). AIM: As the expression of ALU repeat is increased in cancer and has not been assessed in liquid biopsy of cancer patients, our goal was to assess ALU expression in the blood plasma of LABC patients during NAC...
June 26, 2023: Experimental Oncology
https://read.qxmd.com/read/37394769/alu-retrotransposition-event-in-spast-gene-as-a-novel-cause-of-hereditary-spastic-paraplegia
#34
JOURNAL ARTICLE
Yi-Jun Chen, Meng-Wen Wang, Yu-Sen Qiu, Ru-Ying Yuan, Ning Wang, Xiang Lin, Wan-Jin Chen
OBJECTIVES: To diagnose the molecular cause of hereditary spastic paraplegia (HSP) observed in a four-generation family with autosomal dominant inheritance. METHODS: Multiplex ligation-dependent probe amplification (MLPA), whole-exome sequencing (WES), and RNA sequencing (RNA-seq) of peripheral blood leukocytes were performed. Reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing were used to characterize target regions of SPAST. RESULTS: A 121-bp AluYb9 insertion with a 30-bp poly-A tail flanked by 15-bp direct repeats on both sides was identified in the edge of intron 16 in SPAST that segregated with the disease phenotype...
July 2, 2023: Movement Disorders: Official Journal of the Movement Disorder Society
https://read.qxmd.com/read/37372948/crisiss-a-novel-transcriptionally-and-post-translationally-inducible-crispr-cas9-based-cellular-suicide-switch
#35
JOURNAL ARTICLE
Maximilian Amberger, Esther Grueso, Zoltán Ivics
With the ever-increasing developing rate of gene and cellular therapy applications and growing accessibility due to products receiving regulatory approval, the need for effective and reliable safety mechanisms to prevent or eliminate potentially fatal side effects is of the utmost importance. In this study, we present the CRISPR-induced suicide switch (CRISISS) as a tool to eliminate genetically modified cells in an inducible and highly efficient manner by targeting Cas9 to highly repetitive Alu retrotransposons in the human genome, causing irreparable genomic fragmentation by the Cas9 nuclease and resulting cell death...
June 6, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37334706/hsa_circrna_0000284-acts-as-a-cerna-to-participate-in-coronary-heart-disease-progression-by-sponging-mirna-338-3p-via-regulating-the-expression-of-ets1
#36
JOURNAL ARTICLE
PhongSon Dinh, ChauMyThanh Tran, ThiPhuongHoai Dinh, Awais Ali, ShangLing Pan
Coronary heart disease (CHD) is a prevalent global cause of death. Research suggests that circular RNAs (circRNAs) play a role in the development of CHD. In this study, we investigated the expression of hsa_circRNA_0000284 in peripheral blood leukocytes (PBLs) obtained from a cohort of 94 CHD patients aged over 50 years, as well as 126 age-matched healthy controls (HC). An in vitro inflammatory and oxidative injury cell model that simulates CHD was used to evaluate changes in hsa_ circRNA _0000284 under stress...
June 19, 2023: Journal of Biomolecular Structure & Dynamics
https://read.qxmd.com/read/37315561/sine-rna-of-the-imprinted-mirna-clusters-mediates-constitutive-type-iii-interferon-expression-and-antiviral-protection-in-hemochorial-placentas
#37
JOURNAL ARTICLE
Ishani Wickramage, Jeffrey VanWye, Klaas Max, John H Lockhart, Ismet Hortu, Ezinne F Mong, John Canfield, Hiran M Lamabadu Warnakulasuriya Patabendige, Ozlem Guzeloglu-Kayisli, Kimiko Inoue, Atsuo Ogura, Charles J Lockwood, Kemal M Akat, Thomas Tuschl, Umit A Kayisli, Hana Totary-Jain
Hemochorial placentas have evolved defense mechanisms to prevent the vertical transmission of viruses to the immunologically underdeveloped fetus. Unlike somatic cells that require pathogen-associated molecular patterns to stimulate interferon production, placental trophoblasts constitutively produce type III interferons (IFNL) through an unknown mechanism. We demonstrate that transcripts of short interspersed nuclear elements (SINEs) embedded in miRNA clusters within the placenta trigger a viral mimicry response that induces IFNL and confers antiviral protection...
June 7, 2023: Cell Host & Microbe
https://read.qxmd.com/read/37309897/alu-rna-fold-links-splicing-with-signal-recognition-particle-proteins
#38
JOURNAL ARTICLE
Ivana Borovská, Igor Vořechovský, Jana Královičová
Transcriptomic diversity in primates was considerably expanded by exonizations of intronic Alu elements. To better understand their cellular mechanisms we have used structure-based mutagenesis coupled with functional and proteomic assays to study the impact of successive primate mutations and their combinations on inclusion of a sense-oriented AluJ exon in the human F8 gene. We show that the splicing outcome was better predicted by consecutive RNA conformation changes than by computationally derived splicing regulatory motifs...
June 13, 2023: Nucleic Acids Research
https://read.qxmd.com/read/37272871/th1-cells-alter-the-inflammatory-signature-of-il-6-by-channeling-stat-transcription-factors-to-alu-like-retroelements
#39
JOURNAL ARTICLE
David Millrine, Ana Cardus Figueras, Javier Uceda Fernandez, Robert Andrews, Barbara Szomolay, Benjamin C Cossins, Christopher M Rice, Jasmine Li, Victoria J Tyrrell, Louise McLeod, Peter Holmans, Valerie B O'Donnell, Philip R Taylor, Stephen J Turner, Brendan J Jenkins, Gareth W Jones, Nicholas Topley, Nigel M Williams, Simon A Jones
Cytokines that signal via STAT1 and STAT3 transcription factors instruct decisions affecting tissue homeostasis, antimicrobial host defense, and inflammation-induced tissue injury. To understand the coordination of these activities, we applied RNA sequencing, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing to identify the transcriptional output of STAT1 and STAT3 in peritoneal tissues from mice during acute resolving inflammation and inflammation primed to drive fibrosis...
June 5, 2023: Journal of Immunology
https://read.qxmd.com/read/37259223/the-implication-of-alu-cdna-in-the-pathogenesis-of-armd
#40
JOURNAL ARTICLE
Ali Nouraeinejad
Age-related macular degeneration (ARMD or AMD) is a progressive, sight-threatening disease. The pathogenesis of ARMD is complex, involving many factors, such as metabolic, functional, genetic, and environmental factors. Recently, long interspersed nuclear element-1 (L1)-mediated reverse transcription (RT) of Alu RNA into cytoplasmic Alu complementary DNA (cDNA) has been associated with retinal pigment epithelium (RPE) destruction. These findings provide a strong input for a new direction in the management of ARMD, as certain human immunodeficiency virus (HIV) drugs, such as nucleoside reverse transcriptase inhibitors (NRTIs), were found to suppress inflammation and protect cells of the retina...
May 30, 2023: Current Aging Science
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