Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease

Fernandes, Juliane Cristina Ribeiro; Acuña, Stephanie Maia; Aoki, Juliana Ide; Flöeter-Winter, Lucile Maria; Muxel, Sandra Márcia

doi:10.3390/ncrna5010017

Cited by 510 publications

(426 citation statements)

References 213 publications

(237 reference statements)

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“…The first SNP (at 152 mb) was located in the intronic region of a long non‐coding RNA gene (lncRNA; ENSECAG00000036544) and the second SNP (at 153 mb) was located in the intronic region of the aquarius intron‐binding spliceosomal factor gene ( AQR ). In human, lncRNAs are known to play a major role in gene regulation, including the regulation of alternative splicing and their dysfunction may have an impact on several pathologies and diseases (Fernandes, Acuña, Aoki, Floeter‐Winter, & Muxel, ; Romero‐Barrios, Legascue, Benhamed, Ariel, & Crespi, ). Alternative splicing is prevalent in the mammalian immune system to control lymphocyte homeostasis (Yabas, Elliott, & Hoyne, ).…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide association study for insect bite hypersensitivity susceptibility in horses revealed novel associated loci on chromosome 1

Shrestha

Solé

Ducro

et al. 2019

J Animal Breeding Genetics

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Equine insect bite hypersensitivity (IBH) is a pruritic skin allergy caused primarily by biting midges, Culicoides spp. IBH susceptibility has polygenic inheritance and occurs at high frequencies in several horse breeds worldwide, causing increased costs and reduced welfare of affected horses. The aim of this study was to identify and validate single nucleotide polymorphisms (SNPs) associated with equine IBH susceptibility. After quality control, 33,523 SNPs were included in a Bayesian genome‐wide association study on 177 affected and 178 unaffected Icelandic horses. We report associated regions in E. caballus (ECA) 1, 3, 15 and 18, overlapping with known IBH QTLs in horses, and novel regions containing several genes, together explaining 11.46% of the total genetic variance. For validation, three SNPs on ECA 1 and ECA X (explaining the largest percentage of genetic variance) within 1‐mb genomic windows for IBH were genotyped in an independent population of 280 Exmoor ponies. The associated genomic region (152–153 mb) on ECA 1 was confirmed in Exmoor ponies and contains the AQR gene involved in splicing processes and a long non‐coding RNA. This study confirms the polygenic nature of IBH susceptibility and suggests a role of transcriptional regulatory mechanisms (e.g., alternative splicing) for IBH predisposition in these horse breeds.

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Section: Discussionmentioning

confidence: 99%

Genome‐wide association study for insect bite hypersensitivity susceptibility in horses revealed novel associated loci on chromosome 1

Shrestha

Solé

Ducro

et al. 2019

J Animal Breeding Genetics

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“…9 Various diseases including cancer, cardiovascular diseases and neurodegenerative diseases were found to involve in the dysregulated lncRNAs. 10 In the aspect of atherosclerosis, lncRNA retinal non-coding RNA 3 knockdown promoted atherosclerosis by enhancing endothelial cell and VSMC proliferation. 11 The lncRNA UCA1 was up-regulated in oxidized low-density lipoprotein (ox-LDL)-stimulated VSMCs and promoted VSMC migration and proliferation via suppressing miR-26a expression, 12 which contributed to the development of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

LncRNA TNK2‐AS1 regulated ox‐LDL‐stimulated HASMC proliferation and migration via modulating VEGFA and FGF1 expression by sponging miR‐150‐5p

Cai

Cui

Zhang

et al. 2019

J Cellular Molecular Medi

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Long non‐coding RNAs (lncRNAs) have been indicated for the regulatory roles in cardiovascular diseases. This study determined the expression of lncRNA TNK2 antisense RNA 1 (TNK2‐AS1) in oxidized low‐density lipoprotein (ox‐LDL)‐stimulated human aortic smooth muscle cells (HASMCs) and examined the mechanistic role of TNK2‐AS1 in the proliferation and migration of HASMCs. Our results demonstrated that ox‐LDL promoted HASMC proliferation and migration, and the enhanced proliferation and migration in ox‐LDL‐treated HASMCs were accompanied by the up‐regulation of TNK2‐AS1. In vitro functional studies showed that TNK2‐AS1 knockdown suppressed cell proliferation and migration of ox‐LDL‐stimulated HASMCs, while TNK2‐AS1 overexpression enhanced HASMC proliferation and migration. Additionally, TNK2‐AS1 inversely regulated miR‐150‐5p expression via acting as a competing endogenous RNA (ceRNA), and the enhanced effects of TNK2‐AS1 overexpression on HASMC proliferation and migration were attenuated by miR‐150‐5p overexpression. Moreover, miR‐150‐5p could target the 3’ untranslated regions of vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) to regulate FGF1 and VEGFA expression in HASMCs, and the inhibitory effects of miR‐150‐5p overexpression in ox‐LDL‐stimulated HASMCs were attenuated by enforced expression of VEGFA and FGF1. Enforced expression of VEGFA and FGF1 also partially restored the suppressed cell proliferation and migration induced by TNK2‐AS1 knockdown in ox‐LDL‐stimulated HASMCs, while the enhanced effects of TNK2‐AS1 overexpression on HASMC proliferation and migration were attenuated by the knockdown of VEGFA and FGF1. Collectively, our findings showed that TNK2‐AS1 exerted its action in ox‐LDL‐stimulated HASMCs via regulating VEGFA and FGF1 expression by acting as a ceRNA for miR‐150‐5p.

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“…Non-coding RNAs appear to be the preponderant part of transcribed genomes in eukaryotes with a regulatory capacity in different physiopathological processes that were described in several manuscripts (see [206] for a review on miRNA function and [207,208] for lncRNAs). It would be interesting to understand their function in cell reprogramming considered results obtained by researchers studying reprogramming cells [156,209].…”

Section: Discussionmentioning

confidence: 99%

A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

Alessio

Bonadio

Buson

et al. 2020

IJMS

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In late 2012 it was evidenced that most of the human genome is transcribed but only a small percentage of the transcripts are translated. This observation supported the importance of non-coding RNAs and it was confirmed in several organisms. The most abundant non-translated transcripts are long non-coding RNAs (lncRNAs). In contrast to protein-coding RNAs, they show a more cell-specific expression. To understand the function of lncRNAs, it is fundamental to investigate in which cells they are preferentially expressed and to detect their subcellular localization. Recent improvements of techniques that localize single RNA molecules in tissues like single-cell RNA sequencing and fluorescence amplification methods have given a considerable boost in the knowledge of the lncRNA functions. In recent years, single-cell transcription variability was associated with non-coding RNA expression, revealing this class of RNAs as important transcripts in the cell lineage specification. The purpose of this review is to collect updated information about lncRNA classification and new findings on their function derived from single-cell analysis. We also retained useful for all researchers to describe the methods available for single-cell analysis and the databases collecting single-cell and lncRNA data. Tables are included to schematize, describe, and compare exposed concepts.Int. J. Mol. Sci. 2020, 21, 302 2 of 32 not achieved by transcription factors (TFs) alone because of their low number (approximately 1500 in mammals [4]) compared to genes to regulate (90% of the genome is transcribed in human [5]). A single TF is estimated to regulate only ten thousand genes according to Chromatin immunoprecipitation and DNA sequencing experiments (ChIp-seq) [6]. Moreover, the involvement of non-coding RNAs in gene expression regulation was evident [7,8]. The evidence that the non-protein coding component of the human genome is actively transcribed and carries out crucial functions limits the importance of coding genes in genome regulation. Non-coding transcripts become one of the stars of modern biology, especially because of their involvement in a wide range of regulatory processes and changed the association of non-coding regions to junk DNA [3].The genome of multicellular eukaryotes is mostly comprised of non-coding DNA (less than 2% of the human genome codes for proteins [9] while 90% of the human genome is transcribed). Non-coding DNA is transcribed into different classes of non-coding RNAs (ncRNAs) that include structural RNAs (rRNAs and tRNAs) and regulatory RNAs [10]. rRNAs and tRNAs are involved in mRNA translation and can be long or short in size. Regulatory RNAs are further divided into three classes: Small, medium, and long non-coding RNAs. Small non-coding RNAs are between 20 and 50 nucleotides long and include microRNAs (miRNAs) that participate in post-transcriptional regulation [11], small interfering RNAs (siRNAs) that are double-stranded RNAs involved in gene silencing through RNA interfering pathway [12], piwi interacting R...

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Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease

Cited by 510 publications

References 213 publications

Genome‐wide association study for insect bite hypersensitivity susceptibility in horses revealed novel associated loci on chromosome 1

Genome‐wide association study for insect bite hypersensitivity susceptibility in horses revealed novel associated loci on chromosome 1

LncRNA TNK2‐AS1 regulated ox‐LDL‐stimulated HASMC proliferation and migration via modulating VEGFA and FGF1 expression by sponging miR‐150‐5p

A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

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