Long Non-coding RNA Signatures Associated With Liver Aging in Senescence-Accelerated Mouse Prone 8 Model

The liver is sensitive to aging because the risk of hepatopathy, including fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, increases dramatically with age. Long non-coding RNAs (lncRNAs) are >200 nucleotides long and affect many pathological and physiological processes. A potential link was recently discovered between lncRNAs and liver aging; however, comprehensive and systematic research on this topic is still limited. In this study, the mouse liver genome-wide lncRNA profiles of 8-month-old SAMP8 and SAMR1 models were explored through deep RNA sequencing. A total of 605,801,688 clean reads were generated. Among the 2,182 identified lncRNAs, 28 were differentially expressed between SAMP8 and SAMR1 mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) surveys showed that these substantially dysregulated lncRNAs participated in liver aging from different aspects, such as lipid catabolic (GO: 0016042) and metabolic pathways. Further assessment was conducted on lncRNAs that are most likely to be involved in liver aging and related diseases, such as LNC_000027, LNC_000204E, NSMUST00000144661.1, and ENSMUST00000181906.1 acted on Ces1g. This study provided the first comprehensive dissection of lncRNA landscape in SAMP8 mouse liver. These lncRNAs could be exploited as potential targets for the molecular-based diagnosis and therapy of age-related liver diseases.

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Long Non-Coding RNAs as Endogenous Target Mimics and Exploration of Their Role in Low Nutrient Stress Tolerance in Plants

Genes ◽

10.3390/genes9090459 ◽

2018 ◽

Vol 9 (9) ◽

pp. 459 ◽

Cited By ~ 5

Author(s):

Priyanka Borah ◽

Antara Das ◽

Matthew Milner ◽

Arif Ali ◽

Alison Bentley ◽

...

Keyword(s):

Gene Regulation ◽

Next Generation Sequencing ◽

Non Coding Rna ◽

Genome Wide ◽

Non Coding Rnas ◽

Endogenous Target ◽

Long Non Coding Rna ◽

Nutrient Homeostasis ◽

Generation Sequencing

Long non-coding RNA (lncRNA) research in plants has recently gained momentum taking cues from studies in animals systems. The availability of next-generation sequencing has enabled genome-wide identification of lncRNA in several plant species. Some lncRNAs are inhibitors of microRNA expression and have a function known as target mimicry with the sequestered transcript known as an endogenous target mimic (eTM). The lncRNAs identified to date show diverse mechanisms of gene regulation, most of which remain poorly understood. In this review, we discuss the role of identified putative lncRNAs that may act as eTMs for nutrient-responsive microRNAs (miRNAs) in plants. If functionally validated, these putative lncRNAs would enhance current understanding of the role of lncRNAs in nutrient homeostasis in plants.

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Long Non-Coding RNA Expression Profiling in Aging Rats with Erectile Dysfunction

Cellular Physiology and Biochemistry ◽

10.1159/000438519 ◽

2015 ◽

Vol 37 (4) ◽

pp. 1513-1526 ◽

Cited By ~ 10

Author(s):

Lianjun Pan ◽

Jiehua Ma ◽

Feng Pan ◽

Dan Zhao ◽

Jianping Gao

Keyword(s):

Erectile Dysfunction ◽

Expression Profiles ◽

Critical Role ◽

Altered Expression ◽

Aged People ◽

Age Related ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Rna Expression Profiling ◽

Long Non Coding Rna

Background/Aims: Erectile dysfunction (ED) in aged people remains a topic of interest to andrological physicians. Long non-coding RNAs (lncRNAs), which form the largest group of non-coding RNAs, have been shown to regulate various biological processes. The function of lncRNAs in age-related erectile dysfunction (A-ED) pathogenesis remains poorly understood. Methods: This study aims to assess the differential expression profiles of mRNAs and lncRNAs between A-ED and normal control (NC) samples. Using a second-generation lncRNA microarray, we detected a total of 8,744 lncRNAs and 13,585 coding transcripts. Results: We identified 608 up-regulated and 406 down-regulated lncRNAs in A-ED compared with NC samples, by setting a filter of fold-change >2.0. Gene Ontology and pathway analysis revealed that a muscle contraction disorder induced by abnormal ion channels might play a critical role in the pathogenesis of A-ED. Conclusion: Our results show significantly altered expression profiles of lncRNAs and mRNAs between A-ED and NC. This study may provide information for further research on A-ED and may be helpful for finding a new therapeutic target for A-ED.

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Genome-wide identification and characterization of long non-coding RNAs responsive to Dickeya zeae in rice

RSC Advances ◽

10.1039/c8ra04993a ◽

2018 ◽

Vol 8 (60) ◽

pp. 34408-34417 ◽

Cited By ~ 3

Author(s):

Wen Qi Li ◽

Yu Lin Jia ◽

Feng Quan Liu ◽

Fang Quan Wang ◽

Fang Jun Fan ◽

...

Keyword(s):

Stress Responses ◽

Critical Role ◽

Non Coding Rna ◽

Genome Wide ◽

Epigenetic Regulator ◽

Non Coding Rnas ◽

Growth Development ◽

Long Non Coding Rna ◽

Identification And Characterization

Plant long non-coding RNA (lncRNA) is a type of newly emerging epigenetic regulator playing a critical role in plant growth, development, and biotic stress responses.

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Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency

10.1101/2021.02.08.430256 ◽

2021 ◽

Author(s):

Jeffrey R. Haswell ◽

Kaia Mattioli ◽

Chiara Gerhardinger ◽

Philipp G. Maass ◽

Daniel J. Foster ◽

...

Keyword(s):

Embryonic Stem ◽

Functional Screening ◽

Specific Expression ◽

Endoderm Differentiation ◽

Non Coding Rna ◽

Genome Wide ◽

Clustering Approach ◽

Non Coding Rnas ◽

Hesc Lines ◽

Long Non Coding Rna

ABSTRACTAlthough many long non-coding RNAs (lncRNAs) exhibit lineage-specific expression, the vast majority remain functionally uncharacterized in the context of development. Here, we report the first described human embryonic stem cell (hESC) lines to repress (CRISPRi) or activate (CRISPRa) transcription during differentiation into all three germ layers, facilitating the modulation of lncRNA expression during early development. We performed an unbiased, genome-wide CRISPRi screen targeting thousands of lncRNA loci expressed during endoderm differentiation. While dozens of lncRNA loci were required for proper differentiation, most differentially expressed lncRNAs were not, supporting the necessity for functional screening instead of relying solely on gene expression analyses. In parallel, we developed a clustering approach to infer mechanisms of action of lncRNA hits based on a variety of genomic features. We subsequently identified and validated FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. Taken together, the cell lines and methodology described herein can be adapted to discover and characterize novel regulators of differentiation into any lineage.

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Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency

PLoS ONE ◽

10.1371/journal.pone.0252848 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0252848

Author(s):

Jeffrey R. Haswell ◽

Kaia Mattioli ◽

Chiara Gerhardinger ◽

Philipp G. Maass ◽

Daniel J. Foster ◽

...

Keyword(s):

Embryonic Stem ◽

Functional Screening ◽

Specific Expression ◽

Endoderm Differentiation ◽

Non Coding Rna ◽

Genome Wide ◽

Clustering Approach ◽

Non Coding Rnas ◽

Hesc Lines ◽

Long Non Coding Rna

Although many long non-coding RNAs (lncRNAs) exhibit lineage-specific expression, the vast majority remain functionally uncharacterized in the context of development. Here, we report the first described human embryonic stem cell (hESC) lines to repress (CRISPRi) or activate (CRISPRa) transcription during differentiation into all three germ layers, facilitating the modulation of lncRNA expression during early development. We performed an unbiased, genome-wide CRISPRi screen targeting thousands of lncRNA loci expressed during endoderm differentiation. While dozens of lncRNA loci were required for proper differentiation, most differentially expressed lncRNAs were not, supporting the necessity for functional screening instead of relying solely on gene expression analyses. In parallel, we developed a clustering approach to infer mechanisms of action of lncRNA hits based on a variety of genomic features. We subsequently identified and validated FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. Taken together, the cell lines and methodology described herein can be adapted to discover and characterize novel regulators of differentiation into any lineage.

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Pharmacogenomics of Lithium Response in Bipolar Disorder

Pharmaceuticals ◽

10.3390/ph14040287 ◽

2021 ◽

Vol 14 (4) ◽

pp. 287

Author(s):

Courtney M. Vecera ◽

Gabriel R. Fries ◽

Lokesh R. Shahani ◽

Jair C. Soares ◽

Rodrigo Machado-Vieira

Keyword(s):

Bipolar Disorder ◽

Association Studies ◽

Mood Stabilizer ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Non Coding Rna ◽

Genome Wide ◽

Lithium Response ◽

Genetic Loading ◽

Long Non Coding Rna

Despite being the most widely studied mood stabilizer, researchers have not confirmed a mechanism for lithium’s therapeutic efficacy in Bipolar Disorder (BD). Pharmacogenomic applications may be clinically useful in the future for identifying lithium-responsive patients and facilitating personalized treatment. Six genome-wide association studies (GWAS) reviewed here present evidence of genetic variations related to lithium responsivity and side effect expression. Variants were found on genes regulating the glutamate system, including GAD-like gene 1 (GADL1) and GRIA2 gene, a mutually-regulated target of lithium. In addition, single nucleotide polymorphisms (SNPs) discovered on SESTD1 may account for lithium’s exceptional ability to permeate cell membranes and mediate autoimmune and renal effects. Studies also corroborated the importance of epigenetics and stress regulation on lithium response, finding variants on long, non-coding RNA genes and associations between response and genetic loading for psychiatric comorbidities. Overall, the precision medicine model of stratifying patients based on phenotype seems to derive genotypic support of a separate clinical subtype of lithium-responsive BD. Results have yet to be expounded upon and should therefore be interpreted with caution.

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Functional genomics of autoimmune diseases

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2019-216794 ◽

2021 ◽

pp. annrheumdis-2019-216794

Author(s):

Akari Suzuki ◽

Matteo Maurizio Guerrini ◽

Kazuhiko Yamamoto

Keyword(s):

Autoimmune Diseases ◽

Association Studies ◽

Linkage Disequilibrium Block ◽

Causal Variant ◽

Genome Wide Association Studies ◽

Coding Region ◽

Risk Variants ◽

Non Coding Rna ◽

Genome Wide ◽

Long Non Coding Rna

For more than a decade, genome-wide association studies have been applied to autoimmune diseases and have expanded our understanding on the pathogeneses. Genetic risk factors associated with diseases and traits are essentially causative. However, elucidation of the biological mechanism of disease from genetic factors is challenging. In fact, it is difficult to identify the causal variant among multiple variants located on the same haplotype or linkage disequilibrium block and thus the responsible biological genes remain elusive. Recently, multiple studies have revealed that the majority of risk variants locate in the non-coding region of the genome and they are the most likely to regulate gene expression such as quantitative trait loci. Enhancer, promoter and long non-coding RNA appear to be the main target mechanisms of the risk variants. In this review, we discuss functional genetics to challenge these puzzles.

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Long Non-coding RNA FEZF1-AS1 Promotes Growth and Reduces Apoptosis Through Regulation of miR-363-3p/PAX6 Axis in Retinoblastoma

Biochemical Genetics ◽

10.1007/s10528-020-10026-7 ◽

2021 ◽

Author(s):

Xiuming Liu ◽

Xiaofeng Li ◽

Jianchang Li

Keyword(s):

Cell Viability ◽

Antisense Rna ◽

Tumor Formation ◽

Retinoblastoma Cell ◽

Non Coding Rna ◽

High Incidence ◽

Non Coding Rnas ◽

Long Non Coding Rna ◽

Common Malignancy

AbstractRetinoblastoma is the most common malignancy in children's eyes with high incidence. Long non-coding RNAs (lncRNAs) play important roles in the progression of retinoblastoma. LncRNA FEZF1 antisense RNA 1 (FEZF1-AS1) has been found to stimulate retinoblastoma. However, the mechanism of FEZF1-AS1 underlying progression of retinoblastoma is still unclear. In current study, FEZF1-AS1 was up-regulated in retinoblastoma tissues and cells. FEZF1-AS1 overexpression enhanced retinoblastoma cell viability, promoted cell cycle, and inhibited apoptosis. Conversely, FEZF1-AS1 knockdown reduced cell viability, cycle, and elevated apoptosis. The interaction between FEZF1-AS1 and microRNA-363-3p (miR-363-3p) was confirmed. FEZF1-AS1 down-regulated miR-363-3p and up-regulated PAX6. PAX6 was a target gene of miR-363-3p. EZF1-AS1 promoted retinoblastoma cell viability and suppressed apoptosis via PAX6. Further, we demonstrated that FEZF1-AS1 contribute to tumor formation in vivo. In conclusion, FEZF1-AS1 elevated growth and inhibited apoptosis by regulating miR-363-3p/PAX6 in retinoblastoma, which provide a new target for retinoblastoma treatment.

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Integrated Analysis of Long Non-Coding RNA and mRNA Expression Profiles in Testes of Calves and Sexually Mature Wandong Bulls (Bos taurus)

Animals ◽

10.3390/ani11072006 ◽

2021 ◽

Vol 11 (7) ◽

pp. 2006

Author(s):

Hongyu Liu ◽

Ibrar Muhammad Khan ◽

Huiqun Yin ◽

Xinqi Zhou ◽

Muhammad Rizwan ◽

...

Keyword(s):

Target Genes ◽

Expression Profiles ◽

Age Groups ◽

Adherens Junction ◽

Integrated Analysis ◽

Sequencing Data ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Rna Interaction ◽

Long Non Coding Rna

The mRNAs and long non-coding RNAs axes are playing a vital role in the regulating of post-transcriptional gene expression. Thereby, elucidating the expression pattern of mRNAs and long non-coding RNAs underlying testis development is crucial. In this study, mRNA and long non-coding RNAs expression profiles were investigated in 3-month-old calves and 3-year-old mature bulls’ testes by total RNA sequencing. Additionally, during the gene level analysis, 21,250 mRNAs and 20,533 long non-coding RNAs were identified. As a result, 7908 long non-coding RNAs (p-adjust < 0.05) and 5122 mRNAs (p-adjust < 0.05) were significantly differentially expressed between the distinct age groups. In addition, gene ontology and biological pathway analyses revealed that the predicted target genes are enriched in the lysine degradation, cell cycle, propanoate metabolism, adherens junction and cell adhesion molecules pathways. Correspondingly, the RT-qPCR validation results showed a strong consistency with the sequencing data. The source genes for the mRNAs (CCDC83, DMRTC2, HSPA2, IQCG, PACRG, SPO11, EHHADH, SPP1, NSD2 and ACTN4) and the long non-coding RNAs (COX7A2, COX6B2, TRIM37, PRM2, INHBA, ERBB4, SDHA, ATP6VOA2, FGF9 and TCF21) were found to be actively associated with bull sexual maturity and spermatogenesis. This study provided a comprehensive catalog of long non-coding RNAs in the bovine testes and also offered useful resources for understanding the differences in sexual development caused by the changes in the mRNA and long non-coding RNA interaction expressions between the immature and mature stages.

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