scholarly journals Dysregulation of Long Non-coding RNA (lncRNA) Genes and Predicted lncRNA-Protein Interactions during Zika Virus Infection

2016 ◽  
Author(s):  
Arunachalam Ramaiah ◽  
Deisy Contreras ◽  
Vineela Gangalapudi ◽  
Masumi Sameer Padhye ◽  
Jie Tang ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Zika Virus ◽  
Mammalian Cells ◽  
Noncoding Rna ◽  
Target Genes ◽  
Vero Cells ◽  
Viral Pathogens ◽  
Developmental Abnormalities ◽  
Non Coding Rna ◽  
Cellular Factors

ABSTRACTZika Virus (ZIKV) is a causative agent for poor pregnancy outcome and fetal developmental abnormalities, including microcephaly and eye defects. As a result, ZIKV is now a confirmed teratogen. Understanding host-pathogen interactions, specifically cellular perturbations caused by ZIKV, can provide novel therapeutic targets. In order to complete viral replication, viral pathogens control the host cellular machineries and regulate various factors, including long noncoding RNA (lncRNA) genes, at transcriptional levels. The role of lncRNA genes in the pathogenesis of ZIKV-mediated microcephaly and eye defects is currently unknown. To gain additional insights, we focused on profiling the differentially expressed lncRNA genes during ZIKV infection in mammalian cells. For this study, we employed a contemporary clinical Zika viral isolate, PRVABC59, of Asian genotype. We utilized an unbiased RNA sequencing approach to profile the lncRNA transcriptome in ZIKV infected Vero cells. We identified a total of 121 lncRNA genes that are differentially regulated at 48 hours post-infection. The majority of these genes are independently validated by reverse-transcription qPCR. A notable observation was that the lncRNAs, MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and NEAT1 (Nuclear Paraspeckle Assembly Transcript 1), are down-regulated upon Zika viral infection. MALAT1 and NEAT1 are known as nuclear localized RNAs that regulate gene expression and cell proliferation. Protein-lncRNA interaction maps revealed that MALAT1 and NEAT1 share common interacting partners and form a larger network comprising of 71 cellular factors. ZIKV-mediated dysregulation of these two regulatory lncRNAs can alter the expression of respective target genes and associated biological functions, an important one being cell division. In conclusion, this investigation is the first to provide insight into the biological connection of lncRNAs and ZIKV which can be further explored for developing antiviral therapy and understanding fetal developmental processes.

scholarly journals Enzymatic RNA Biotinylation for Affinity Purification and Identification of RNA-protein Interactions

2020 ◽  
Author(s):  
Kayla N. Busby ◽  
Amitkumar Fulzele ◽  
Dongyang Zhang ◽  
Eric J. Bennett ◽  
Neal K. Devaraj
Keyword(s):  
Protein Interactions ◽  
Mammalian Cells ◽  
Noncoding Rna ◽  
Affinity Purification ◽  
Functional Characterization ◽  
Selective Enrichment ◽  
Binding Partners ◽  
Nucleotide Mutation ◽  
Rna Biology ◽  
And Function

ABSTRACTThroughout their cellular lifetime, RNA transcripts are bound to proteins, playing crucial roles in RNA metabolism, trafficking, and function. Despite the importance of these interactions, identifying the proteins that interact with an RNA of interest in mammalian cells represents a major challenge in RNA biology. Leveraging the ability to site-specifically and covalently label an RNA of interest using E. Coli tRNA guanine transglycosylase and an unnatural nucleobase substrate, we establish the identification of RNA-protein interactions and the selective enrichment of cellular RNA in mammalian systems. We demonstrate the utility of this approach through the identification of known binding partners of 7SK snRNA via mass spectrometry. Through a minimal 4-nucleotide mutation of the long noncoding RNA HOTAIR, enzymatic biotinylation enables identification putative HOTAIR binding partners in MCF7 breast cancer cells that suggest new potential pathways for oncogenic function. Furthermore, using RNA sequencing and qPCR, we establish that an engineered enzyme variant achieves high levels of labeling selectivity against the human transcriptome allowing for 145-fold enrichment of cellular RNA directly from mammalian cell lysates. The flexibility and breadth of this approach suggests that this system could be routinely applied to the functional characterization of RNA, greatly expanding the toolbox available for studying mammalian RNA biology.

scholarly journals The long noncoding RNA-30162 is regulated by commensal microbiota and modulates CCL24 and ARG1 in macrophages

2020 ◽  
Author(s):  
Yingjie Mu ◽  
Wen Chen ◽  
Shilian Hu ◽  
Min Cheng
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Noncoding Rna ◽  
Target Genes ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Commensal Microbiota ◽  
Non Coding Rna ◽  
Distal Lung ◽  
Long Non Coding Rna

Abstract Background Alveolar macrophages (AMs) are the largest number of innate immune cells in the distal lung. AMs have critical roles in maintaining immunological homoeostasis and host defense in the lung and are inherently suppressive. Immune homeostasis depends on the integrity of microbiome, which contribute to appropriate maturation and priming of the immune system. The absence of commensal microbiota can lead to changes in AM function; however, little is known about the effect of long non-coding RNA (lncRNA) molecules in this process. Results Here, by lncRNA microarray analysis using AM samples from antibiotic-treated (Abt) mice, we found that treatment with antibiotics resulted in differential expression of numerous lncRNAs in AMs. Target genes of differentially expressed lncRNAs were associated with several biological pathways, including regulation of immune system processes, angiogenesis, cell differentiation, and chemotaxis, among others. Notably, lncRNA-30162 expression levels were up-regulated in AMs from Abt mice. Moreover, knockdown of lncRNA-30162 expression significantly reduced CCL24 and ARG1 levels in macrophages. Conclusions These findings indicate that microbiome can regulate the expression of lncRNA-30162 in AMs, identifying a molecular mechanism underlying lncRNA-mediated regulation of macrophage functions.

scholarly journals Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells

2001 ◽  
Vol 21 (10) ◽  
pp. 3589-3597 ◽  
Author(s):  
Keri Fair ◽  
Melanie Anderson ◽  
Elena Bulanova ◽  
Huaifeng Mi ◽  
Maximilian Tropschug ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Protein Interactions ◽  
Mammalian Cells ◽  
Target Gene ◽  
Target Genes ◽  
Leukemia Cells ◽  
Altered Expression ◽  
Amino Acid Sequence Conservation

ABSTRACT The PHD fingers of the human MLL and Drosophila trx proteins have strong amino acid sequence conservation but their function is unknown. We have determined that these fingers mediate homodimerization and binding of MLL to Cyp33, a nuclear cyclophilin. These two proteins interact in vitro and in vivo in mammalian cells and colocalize at specific nuclear subdomains. Overexpression of the Cyp33 protein in leukemia cells results in altered expression ofHOX genes that are targets for regulation by MLL. These alterations are suppressed by cyclosporine and are not observed in cell lines that express a mutant MLL protein without PHD fingers. These results suggest that binding of Cyp33 to MLL modulates its effects on the expression of target genes.

scholarly journals DeepciRGO: functional prediction of circular RNAs through hierarchical deep neural networks using heterogeneous network features

2020 ◽  
Author(s):  
Lei Deng ◽  
Wei Lin ◽  
Jiacheng Wang ◽  
Jingpu Zhang
Keyword(s):  
Gene Ontology ◽  
Protein Interactions ◽  
Heterogeneous Network ◽  
Mammalian Cells ◽  
Noncoding Rna ◽  
Large Scale ◽  
Hierarchical Classification ◽  
Representation Learning ◽  
Classification Model ◽  
Circular Rnas

Abstract Circular RNAs (circRNAs) are special noncoding RNA molecules with closed loop structures. Compared with the traditional linear RNA, circRNA is more stable and not easily degraded. Many studies have shown that circRNAs are involved in the regulation of various diseases and cancers. Determining the functions of circRNAs in mammalian cells is of great significance for revealing their mechanism of action in physiological and pathological processes, diagnosis and treatment of diseases. However, determining the functions of circRNAs on a large scale is a challenging task because of the high experimental costs. In this paper, we present a hierarchical deep learning model, DeepciRGO, which can effectively predict gene ontology functions of circRNAs. We build a heterogeneous network containing circRNA co-expressions, protein-protein interactions (PPIs) and protein-circRNA interactions. The topology features of proteins and circRNAs are calculated using a novel representation learning approach Hin2vec across the heterogeneous network. Then, a deep multi-label hierarchical classification model is trained with the topology features to predict the biological process (BP) function in the Gene Ontology (GO) for each circRNA. In particular, we manually curated a benchmark dataset containing 185 GO annotations for 62 circRNAs, namely, circRNA2GO-62. The DeepciRGO achieves promising performance on the circRNA2GO-62 dataset with a maximum F-measure of 0.412, a recall score of 0.4, and an accuracy of 0.4, which are significantly better than other state-of-the-art RNA function prediction methods. In addition, we demonstrate the considerable potential of integrating multiple interactions and association networks.

scholarly journals Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen

2015 ◽  
Vol 20 (9) ◽  
pp. 1132-1141 ◽  
Author(s):  
Roya Pedram Fatemi ◽  
Sultan Salah-Uddin ◽  
Farzaneh Modarresi ◽  
Nathalie Khoury ◽  
Claes Wahlestedt ◽  
...  
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Protein Interactions ◽  
High Throughput Screening ◽  
Noncoding Rna ◽  
Target Genes ◽  
Regulatory Function ◽  
Downstream Target ◽  
Small Molecule Modulators ◽  
In Cells

Long non–protein coding RNAs (lncRNAs) are an important class of molecules that help orchestrate key cellular events. Although their functional roles in cells are not well understood, thousands of lncRNAs and a number of possible mechanisms by which they act have been reported. LncRNAs can exert their regulatory function in cells by interacting with epigenetic enzymes. In this study, we developed a tool to study lncRNA-protein interactions for high-throughput screening of small-molecule modulators using AlphaScreen technology. We tested the interaction of two lncRNAs: brain-derived neurotrophic factor antisense ( BDNF-AS) and Hox transcript antisense RNA ( HOTAIR), with Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase against a phytochemical library, to look for small-molecule inhibitors that can alter the expression of downstream target genes. We identified ellipticine, a compound that up-regulates BDNF transcription. Our study shows the feasibility of using high-throughput screening to identify modulators of lncRNA-protein interactions and paves the road for targeting lncRNAs that are dysregulated in human disorders using small-molecule therapies.

Recent Advances on the Semi-Supervised Learning for Long Non-Coding RNA-Protein Interactions Prediction: A Review

2020 ◽  
Vol 27 (5) ◽  
pp. 385-391
Author(s):  
Lin Zhong ◽  
Zhong Ming ◽  
Guobo Xie ◽  
Chunlong Fan ◽  
Xue Piao
Keyword(s):  
Supervised Learning ◽  
Protein Interactions ◽  
Computational Models ◽  
Prediction Models ◽  
Chromatin Modification ◽  
Computational Prediction ◽  
Human Diseases ◽  
Future Research ◽  
Non Coding Rna ◽  
Long Non Coding Rna

: In recent years, more and more evidence indicates that long non-coding RNA (lncRNA) plays a significant role in the development of complex biological processes, especially in RNA progressing, chromatin modification, and cell differentiation, as well as many other processes. Surprisingly, lncRNA has an inseparable relationship with human diseases such as cancer. Therefore, only by knowing more about the function of lncRNA can we better solve the problems of human diseases. However, lncRNAs need to bind to proteins to perform their biomedical functions. So we can reveal the lncRNA function by studying the relationship between lncRNA and protein. But due to the limitations of traditional experiments, researchers often use computational prediction models to predict lncRNA protein interactions. In this review, we summarize several computational models of the lncRNA protein interactions prediction base on semi-supervised learning during the past two years, and introduce their advantages and shortcomings briefly. Finally, the future research directions of lncRNA protein interaction prediction are pointed out.

The P-MAPA immunomodulator partially prevents apoptosis induced by Zika virus infection in THP-1 cells

2020 ◽  
Vol 21 ◽  
Author(s):  
Morganna C. Lima ◽  
Elisa A. N. Azevedo ◽  
Clarice N. L. de Morais ◽  
Larissa I. O. de Sousa ◽  
Bruno M. Carvalho ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Virus Infection ◽  
Virus Replication ◽  
Zika Virus ◽  
Mammalian Cells ◽  
Caspase 3 ◽  
Neurological Complications ◽  
Zika Virus Infection

Background: Zika virus is an emerging arbovirus of global importance. ZIKV infection is associated with a range of neurological complications such as the Congenital Zika Syndrome and Guillain Barré Syndrome. Despite the magnitude of recent outbreaks, there is no specific therapy to prevent or to alleviate disease pathology. Objective: To investigate the role of P-MAPA immunomodulator in Zika-infected THP-1 cells. Methods: THP-1 cells were subjected at Zika virus infection (Multiplicity of Infection = 0.5) followed by treatment with P-MAPA for until 96 hours post-infection. After that, the cell death was analyzed by annexin+/ PI+ and caspase 3/ 7+ staining by flow cytometry. In addition, the virus replication and cell proliferation were accessed by RT-qPCR and Ki67 staining, respectively. Results: We demonstrate that P-MAPA in vitro treatment significantly reduces Zika virus-induced cell death and caspase-3/7 activation on THP-1 infected cells, albeit it has no role in virus replication and cell proliferation. Conclusions: Our study reveals that P-MAPA seems to be a satisfactory alternative to inhibits the effects of Zika virus infection in mammalian cells.

scholarly journals Small Non-Coding-RNA in Gynecological Malignancies

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1085
Author(s):  
Shailendra Kumar Dhar Dwivedi ◽  
Geeta Rao ◽  
Anindya Dey ◽  
Priyabrata Mukherjee ◽  
Jonathan D. Wren ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
P Element ◽  
Gynecologic Malignancies ◽  
Diagnosis And Prognosis ◽  
Gynecological Malignancies ◽  
Non Coding Rna ◽  
Therapeutic Research ◽  
Regulatory Functions

Gynecologic malignancies, which include cancers of the cervix, ovary, uterus, vulva, vagina, and fallopian tube, are among the leading causes of female mortality worldwide, with the most prevalent being endometrial, ovarian, and cervical cancer. Gynecologic malignancies are complex, heterogeneous diseases, and despite extensive research efforts, the molecular mechanisms underlying their development and pathology remain largely unclear. Currently, mechanistic and therapeutic research in cancer is largely focused on protein targets that are encoded by about 1% of the human genome. Our current understanding of 99% of the genome, which includes noncoding RNA, is limited. The discovery of tens of thousands of noncoding RNAs (ncRNAs), possessing either structural or regulatory functions, has fundamentally altered our understanding of genetics, physiology, pathophysiology, and disease treatment as they relate to gynecologic malignancies. In recent years, it has become clear that ncRNAs are relatively stable, and can serve as biomarkers for cancer diagnosis and prognosis, as well as guide therapy choices. Here we discuss the role of small non-coding RNAs, i.e., microRNAs (miRs), P-Element induced wimpy testis interacting (PIWI) RNAs (piRNAs), and tRNA-derived small RNAs in gynecological malignancies, specifically focusing on ovarian, endometrial, and cervical cancer.

scholarly journals Dynamic characteristics and functional analysis provide new insights into long non-coding RNA responsive to Verticillium dahliae infection in Gossypium hirsutum

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guoning Wang ◽  
Xingfen Wang ◽  
Yan Zhang ◽  
Jun Yang ◽  
Zhikun Li ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Verticillium Wilt ◽  
Dynamic Characteristics ◽  
Target Genes ◽  
Acid Metabolism ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Alpha Linolenic Acid ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background Verticillium wilt is a widespread and destructive disease, which causes serious loss of cotton yield and quality. Long non-coding RNA (lncRNA) is involved in many biological processes, such as plant disease resistance response, through a variety of regulatory mechanisms, but their possible roles in cotton against Verticillium dahliae infection remain largely unclear. Results Here, we measured the transcriptome of resistant G. hirsutum following infection by V. dahliae and 4277 differentially expressed lncRNAs (delncRNAs) were identified. Localization and abundance analysis revealed that delncRNAs were biased distribution on chromosomes. We explored the dynamic characteristics of disease resistance related lncRNAs in chromosome distribution, induced expression profiles, biological function, and these lncRNAs were divided into three categories according to their induced expression profiles. For the delncRNAs, 687 cis-acting pairs and 14,600 trans-acting pairs of lncRNA-mRNA were identified, which indicated that trans-acting was the main way of Verticillium wilt resistance-associated lncRNAs regulating target mRNAs in cotton. Analyzing the regulation pattern of delncRNAs revealed that cis-acting and trans-acting lncRNAs had different ways to influence target genes. Gene Ontology (GO) enrichment analysis revealed that the regulatory function of delncRNAs participated significantly in stimulus response process, kinase activity and plasma membrane components. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that delncRNAs participated in some important disease resistance pathways, such as plant-pathogen interaction, alpha-linolenic acid metabolism and plant hormone signal transduction. Additionally, 21 delncRNAs and 10 target genes were identified as being involved in alpha-linolenic acid metabolism associated with the biosynthesis of jasmonic acid (JA). Subsequently, we found that GhlncLOX3 might regulate resistance to V. dahliae through modulating the expression of GhLOX3 implicated in JA biosynthesis. Further functional analysis showed that GhlncLOX3-silenced seedlings displayed a reduced resistance to V. dahliae, with down-regulated expression of GhLOX3 and decreased content of JA. Conclusion This study shows the dynamic characteristics of delncRNAs in multiaspect, and suggests that GhlncLOX3-GhLOX3-JA network participates in response to V. dahliae invasion. Our results provide novel insights for genetic improvement of Verticillium wilt resistance in cotton using lncRNAs.

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