scholarly journals Global Analysis of Expression, Maturation and Subcellular Localization of Mouse Liver Transcriptome Identifies Novel Sex-biased and TCPOBOP-responsive Long Non-coding RNAs

2021 ◽  
Author(s):  
Christine Goldfarb ◽  
David Waxman
Keyword(s):  
Mouse Liver ◽  
Global Analysis ◽  
Constitutive Androstane Receptor ◽  
Protein Coding ◽  
Transcript Processing ◽  
Topologically Associating Domains ◽  
Liver Transcriptome ◽  
Non Coding Rnas ◽  
Density Ratios ◽  
Exonic Sequence

Abstract Background: While nuclear transcription and RNA processing and localization are well established for protein coding genes (PCGs), these processes are poorly understood for lncRNAs. Here, we characterize global patterns of transcript expression, maturation and localization for mouse liver RNA, including more than 15,000 lncRNAs. PolyA-selected liver RNA was isolated and sequenced from four subcellular fractions (chromatin, nucleoplasm, total nucleus, and cytoplasm), and from the chromatin-bound fraction without polyA selection.Results: Transcript processing, determined from normalized intronic to exonic sequence read density ratios, progressively increased for PCG transcripts in going from the chromatin-bound fraction to the nucleoplasm and then on to the cytoplasm. Transcript maturation was similar for lncRNAs in the chromatin fraction, but was significantly lower in the nucleoplasm and cytoplasm. LncRNAs were 11-fold more likely to be significantly enriched in the nucleus than cytoplasm, and 100-fold more likely to be significantly chromatin-bound than nucleoplasmic. Sequencing chromatin-bound RNA greatly increased the sensitivity for detecting lowly expressed lncRNAs and enabled us to discover and localize hundreds of novel regulated liver lncRNAs, including lncRNAs showing sex-biased expression or responsiveness to a xenobiotic agonist ligand of constitutive androstane receptor (Nr1i3). Conclusions: Integration of our findings with prior studies and lncRNA annotations identified candidate regulatory lncRNAs for a variety of hepatic functions based on gene co-localization within topologically associating domains or transcription divergent or antisense to PCGs associated with pathways linked to hepatic physiology and disease.

scholarly journals Global analysis of expression, maturation and subcellular localization of mouse liver transcriptome identifies novel sex-biased and TCPOBOP-responsive long non-coding RNAs

2021 ◽  
Author(s):  
Christine N. Goldfarb ◽  
David J. Waxman
Keyword(s):  
Mouse Liver ◽  
Global Analysis ◽  
Constitutive Androstane Receptor ◽  
Protein Coding ◽  
Transcript Processing ◽  
Topologically Associating Domains ◽  
Liver Transcriptome ◽  
Non Coding Rnas ◽  
Density Ratios ◽  
Exonic Sequence

AbstractWhile nuclear transcription and RNA processing and localization are well established for protein coding genes (PCGs), these processes are poorly understood for lncRNAs. Here, we characterize global patterns of transcript expression, maturation and localization for mouse liver RNA, including more than 15,000 lncRNAs. PolyA-selected liver RNA was isolated and sequenced from four subcellular fractions (chromatin, nucleoplasm, total nucleus, and cytoplasm), and from the chromatin-bound fraction without polyA selection. Transcript processing, determined from normalized intronic to exonic sequence read density ratios, progressively increased for PCG transcripts in going from the chromatin-bound fraction to the nucleoplasm and then on to the cytoplasm. Transcript maturation was similar for lncRNAs in the chromatin fraction, but was significantly lower in the nucleoplasm and cytoplasm. LncRNAs were 11-fold more likely to be significantly enriched in the nucleus than cytoplasm, and 100-fold more likely to be significantly chromatin-bound than nucleoplasmic. Sequencing chromatin-bound RNA greatly increased the sensitivity for detecting lowly expressed lncRNAs and enabled us to discover and localize hundreds of novel regulated liver lncRNAs, including lncRNAs showing sex-biased expression or responsiveness to a xenobiotic agonist ligand of constitutive androstane receptor (Nr1i3). Integration of our findings with prior studies and lncRNA annotations identified candidate regulatory lncRNAs for a variety of hepatic functions based on gene co-localization within topologically associating domains or transcription divergent or antisense to PCGs associated with pathways linked to hepatic physiology and diseases.

scholarly journals Global analysis of expression, maturation and subcellular localization of mouse liver transcriptome identifies novel sex-biased and TCPOBOP-responsive long non-coding RNAs

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christine N. Goldfarb ◽  
David J. Waxman
Keyword(s):  
Mouse Liver ◽  
Global Analysis ◽  
Constitutive Androstane Receptor ◽  
Protein Coding ◽  
Transcript Processing ◽  
Topologically Associating Domains ◽  
Liver Transcriptome ◽  
Non Coding Rnas ◽  
Density Ratios ◽  
Exonic Sequence

Abstract Background While nuclear transcription and RNA processing and localization are well established for protein coding genes (PCGs), these processes are poorly understood for long non-coding (lnc)RNAs. Here, we characterize global patterns of transcript expression, maturation and localization for mouse liver RNA, including more than 15,000 lncRNAs. PolyA-selected liver RNA was isolated and sequenced from four subcellular fractions (chromatin, nucleoplasm, total nucleus, and cytoplasm), and from the chromatin-bound fraction without polyA selection. Results Transcript processing, determined from normalized intronic to exonic sequence read density ratios, progressively increased for PCG transcripts in going from the chromatin-bound fraction to the nucleoplasm and then on to the cytoplasm. Transcript maturation was similar for lncRNAs in the chromatin fraction, but was significantly lower in the nucleoplasm and cytoplasm. LncRNA transcripts were 11-fold more likely to be significantly enriched in the nucleus than cytoplasm, and 100-fold more likely to be significantly chromatin-bound than nucleoplasmic. Sequencing chromatin-bound RNA greatly increased the sensitivity for detecting lowly expressed lncRNAs and enabled us to discover and localize hundreds of novel regulated liver lncRNAs, including lncRNAs showing sex-biased expression or responsiveness to TCPOBOP a xenobiotic agonist ligand of constitutive androstane receptor (Nr1i3). Conclusions Integration of our findings with prior studies and lncRNA annotations identified candidate regulatory lncRNAs for a variety of hepatic functions based on gene co-localization within topologically associating domains or transcription divergent or antisense to PCGs associated with pathways linked to hepatic physiology and disease.

scholarly journals De Novo Profiling of Long Non-Coding RNAs Involved in MC-LR-Induced Liver Injury in Whitefish: Discovery and Perspectives

2021 ◽  
Vol 22 (2) ◽  
pp. 941
Author(s):  
Maciej Florczyk ◽  
Paweł Brzuzan ◽  
Maciej Woźny
Keyword(s):  
Liver Injury ◽  
Molecular Mechanisms ◽  
Liver Toxicity ◽  
De Novo ◽  
Minimum Free Energy ◽  
Model Organisms ◽  
Coregonus Lavaretus ◽  
Protein Coding ◽  
Liver Transcriptome ◽  
Non Coding Rnas

Microcystin-LR (MC-LR) is a potent hepatotoxin for which a substantial gap in knowledge persists regarding the underlying molecular mechanisms of liver toxicity and injury. Although long non-coding RNAs (lncRNAs) have been extensively studied in model organisms, our knowledge concerning the role of lncRNAs in liver injury is limited. Given that lncRNAs show low levels of sequence conservation, their role becomes even more unclear in non-model organisms without an annotated genome, like whitefish (Coregonus lavaretus). The objective of this study was to discover and profile aberrantly expressed polyadenylated lncRNAs that are involved in MC-LR-induced liver injury in whitefish. Using RNA sequencing (RNA-Seq) data, we de novo assembled a high-quality whitefish liver transcriptome. This enabled us to find 94 differentially expressed (DE) putative evolutionary conserved lncRNAs, such as MALAT1, HOTTIP, HOTAIR or HULC, and 4429 DE putative novel whitefish lncRNAs, which differed from annotated protein-coding transcripts (PCTs) in terms of minimum free energy, guanine-cytosine (GC) base-pair content and length. Additionally, we identified DE non-coding transcripts that might be 3′ autonomous untranslated regions (3′UTRs) of mRNAs. We found both evolutionary conserved lncRNAs as well as novel whitefish lncRNAs that could serve as biomarkers of liver injury.

scholarly journals Investigation of long non-coding RNAs as regulatory players of grapevine response to powdery and downy mildew infection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Garima Bhatia ◽  
Santosh K. Upadhyay ◽  
Anuradha Upadhyay ◽  
Kashmir Singh
Keyword(s):  
Downy Mildew ◽  
Plasmopara Viticola ◽  
Defense Responses ◽  
Protein Coding ◽  
Functional Roles ◽  
Real Time Quantitative Pcr ◽  
Transcriptional Reprogramming ◽  
Sequencing Technologies ◽  
Non Coding Rnas ◽  
Fungal Phytopathogens

Abstract Background Long non-coding RNAs (lncRNAs) are regulatory transcripts of length > 200 nt. Owing to the rapidly progressing RNA-sequencing technologies, lncRNAs are emerging as considerable nodes in the plant antifungal defense networks. Therefore, we investigated their role in Vitis vinifera (grapevine) in response to obligate biotrophic fungal phytopathogens, Erysiphe necator (powdery mildew, PM) and Plasmopara viticola (downy mildew, DM), which impose huge agro-economic burden on grape-growers worldwide. Results Using computational approach based on RNA-seq data, 71 PM- and 83 DM-responsive V. vinifera lncRNAs were identified and comprehensively examined for their putative functional roles in plant defense response. V. vinifera protein coding sequences (CDS) were also profiled based on expression levels, and 1037 PM-responsive and 670 DM-responsive CDS were identified. Next, co-expression analysis-based functional annotation revealed their association with gene ontology (GO) terms for ‘response to stress’, ‘response to biotic stimulus’, ‘immune system process’, etc. Further investigation based on analysis of domains, enzyme classification, pathways enrichment, transcription factors (TFs), interactions with microRNAs (miRNAs), and real-time quantitative PCR of lncRNAs and co-expressing CDS pairs suggested their involvement in modulation of basal and specific defense responses such as: Ca2+-dependent signaling, cell wall reinforcement, reactive oxygen species metabolism, pathogenesis related proteins accumulation, phytohormonal signal transduction, and secondary metabolism. Conclusions Overall, the identified lncRNAs provide insights into the underlying intricacy of grapevine transcriptional reprogramming/post-transcriptional regulation to delay or seize the living cell-dependent pathogen growth. Therefore, in addition to defense-responsive genes such as TFs, the identified lncRNAs can be further examined and leveraged to candidates for biotechnological improvement/breeding to enhance fungal stress resistance in this susceptible fruit crop of economic and nutritional importance.

Detection of Schistosoma mansoni long non-coding RNAs in the infected C57BL/6 mouse liver

2020 ◽  
pp. 108062
Author(s):  
Ester Alves Mota ◽  
Victor Fernandes Oliveira ◽  
Andressa Barban do Patrocínio ◽  
Vanderlei Rodrigues ◽  
Renata Guerra-Sá
Keyword(s):  
Schistosoma Mansoni ◽  
Mouse Liver ◽  
Non Coding Rnas

scholarly journals Non-Coding RNAs as Prognostic Markers for Endometrial Cancer

2021 ◽  
Vol 22 (6) ◽  
pp. 3151 ◽  
Author(s):  
Roberto Piergentili ◽  
Simona Zaami ◽  
Anna Franca Cavaliere ◽  
Fabrizio Signore ◽  
Giovanni Scambia ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Markers ◽  
Classification Systems ◽  
Prognostic Role ◽  
Protein Coding ◽  
Pathological Characteristics ◽  
Epigenetic Events ◽  
Cancer Types ◽  
Non Coding Rnas

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

scholarly journals RNA sequencing of transcriptomes in human brain regions: protein-coding and non-coding RNAs, isoforms and alleles

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Amy Webb ◽  
Audrey C. Papp ◽  
Amanda Curtis ◽  
Leslie C. Newman ◽  
Maciej Pietrzak ◽  
...  
Keyword(s):  
Human Brain ◽  
Rna Sequencing ◽  
Brain Regions ◽  
Protein Coding ◽  
Non Coding Rnas

scholarly journals CALINCA—A Novel Pipeline for the Identification of lncRNAs in Podocyte Disease

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 692
Author(s):  
Sweta Talyan ◽  
Samantha Filipów ◽  
Michael Ignarski ◽  
Magdalena Smieszek ◽  
He Chen ◽  
...  
Keyword(s):  
Cell Biology ◽  
Mammalian Cells ◽  
De Novo ◽  
Depth Information ◽  
Gene Products ◽  
Classical Analysis ◽  
Protein Coding ◽  
Bioinformatic Pipeline ◽  
Non Coding Rnas ◽  
Filtration Unit

Diseases of the renal filtration unit—the glomerulus—are the most common cause of chronic kidney disease. Podocytes are the pivotal cell type for the function of this filter and focal-segmental glomerulosclerosis (FSGS) is a classic example of a podocytopathy leading to proteinuria and glomerular scarring. Currently, no targeted treatment of FSGS is available. This lack of therapeutic strategies is explained by a limited understanding of the defects in podocyte cell biology leading to FSGS. To date, most studies in the field have focused on protein-coding genes and their gene products. However, more than 80% of all transcripts produced by mammalian cells are actually non-coding. Here, long non-coding RNAs (lncRNAs) are a relatively novel class of transcripts and have not been systematically studied in FSGS to date. The appropriate tools to facilitate lncRNA research for the renal scientific community are urgently required due to a row of challenges compared to classical analysis pipelines optimized for coding RNA expression analysis. Here, we present the bioinformatic pipeline CALINCA as a solution for this problem. CALINCA automatically analyzes datasets from murine FSGS models and quantifies both annotated and de novo assembled lncRNAs. In addition, the tool provides in-depth information on podocyte specificity of these lncRNAs, as well as evolutionary conservation and expression in human datasets making this pipeline a crucial basis to lncRNA studies in FSGS.

393 DECONVOLUTING THE COMPLEXITY OF LONG NON-CODING RNAS AND ESOPHAGEAL CARCINOMA FOR POTENTIAL CLINICAL IMPLICATIONS

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Siyuan Luan ◽  
Yushang Yang ◽  
Shouyue Zhang ◽  
Xiaoxi Zeng ◽  
Xin Xiao ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Rapid Development ◽  
Direct Interaction ◽  
Clinical Applications ◽  
Regulatory Mechanisms ◽  
Protein Coding ◽  
Functional Roles ◽  
Cancer Hallmarks ◽  
Clinical Scenarios ◽  
Non Coding Rnas

Abstract   Long non-coding RNAs (lncRNAs), a type of transcriptional products with more than 200 nucleotides in length, have been less characterized compared to protein-coding RNAs so far. However, it is increasingly evident that lncRNAs are key players involved in multiple genetic and epigenetic activities during the carcinogenesis of neoplastic diseases. Currently, accumulating data have pointed out the close connection between lncRNAs and esophageal carcinoma (EC), shedding light on further unravelling the complexity of lncRNAs and EC. Methods In this review, we thoroughly collect the evidence regarding original studies on EC-related lncRNAs by searching in MEDLINE/PubMed, Embase and WOS/SCI. We especially focus on summarizing EC-related lncRNAs based upon more updated evidence, and further discuss their different features from various perspectives, including regulatory mechanisms, functional roles in cancer hallmarks, as well as potential diagnostic and therapeutic applications, which would together reveal the complexity of lncRNAs and EC for potential clinical applications. Results We discuss over thirty EC-related lncRNAs in total, most of which function as oncogenes that promote cancer development, while the others function as tumor suppressors. Regulatory mechanisms included sponging miRNAs, direct interaction with proteins, and exosome visicle-based intercellular communication. Based upon these modes of actions, lncRNAs play multiple roles in cancer hallmarks such as uncontrolled cell growth, evasion of programmed cell death, invasion and metastasis. Moreover, lncRNAs packaged in exosomes have unique potency to serve as diagnostic biomarkers; some lncRNAs show great potential to predict patients' chemical resistance and may be crucial targets to improve chemoradiotherapy and targeted therapy. Conclusion Over the past few years, the research of EC-related lncRNAs maintain obviously rapid development, yet further exploration of exact mechanisms and clinical applications that lncRNAs can offer need to be done. Indeed, LncRNAs hold the promise of being applied in multiple clinical scenarios, especially early diagnosis of EC, improvement of sensitivity to chemotherapy/radiotherapy, and development of small-molecule targeted drugs.

scholarly journals Non-Coding RNAs in Breast Cancer: Intracellular and Intercellular Communication

2018 ◽  
Vol 4 (4) ◽  
pp. 40 ◽  
Author(s):  
Carolyn Klinge
Keyword(s):  
Breast Cancer ◽  
Intercellular Communication ◽  
Intracellular Signaling ◽  
Colorectal Neoplasia ◽  
Breast Tumors ◽  
Estrogen Receptor Α ◽  
Circular Rnas ◽  
Intercellular Signaling ◽  
Protein Coding ◽  
Non Coding Rnas

Non-coding RNAs (ncRNAs) are regulators of intracellular and intercellular signaling in breast cancer. ncRNAs modulate intracellular signaling to control diverse cellular processes, including levels and activity of estrogen receptor α (ERα), proliferation, invasion, migration, apoptosis, and stemness. In addition, ncRNAs can be packaged into exosomes to provide intercellular communication by the transmission of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) to cells locally or systemically. This review provides an overview of the biogenesis and roles of ncRNAs: small nucleolar RNA (snRNA), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), miRNAs, and lncRNAs in breast cancer. Since more is known about the miRNAs and lncRNAs that are expressed in breast tumors, their established targets as oncogenic drivers and tumor suppressors will be reviewed. The focus is on miRNAs and lncRNAs identified in breast tumors, since a number of ncRNAs identified in breast cancer cells are not dysregulated in breast tumors. The identity and putative function of selected lncRNAs increased: nuclear paraspeckle assembly transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), steroid receptor RNA activator 1 (SRA1), colon cancer associated transcript 2 (CCAT2), colorectal neoplasia differentially expressed (CRNDE), myocardial infarction associated transcript (MIAT), and long intergenic non-protein coding RNA, Regulator of Reprogramming (LINC-ROR); and decreased levels of maternally-expressed 3 (MEG3) in breast tumors have been observed as well. miRNAs and lncRNAs are considered targets of therapeutic intervention in breast cancer, but further work is needed to bring the promise of regulating their activities to clinical use.

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