Long non-coding RNAs: Mechanism of action and functional utility

Bhat, Sajad Ahmad; Ahmad, Syed Mudasir; Mumtaz, Peerzada Tajamul; Malik, Abrar; Dar, Muneer Ahmad; Urwat, Uneeb; Shah, Riaz Ahmad; Ganai, Nazir Ahmad

doi:10.1016/j.ncrna.2016.11.002

Cited by 208 publications

(175 citation statements)

References 113 publications

(150 reference statements)

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“…Noncoding RNAs (such as KCNQ1OT1, MALAT1, and HOTAIR) often act as chromatin regulators, bind to TFs to regulate the expression of the nearest protein‐coding genes, can identify complementary regions, and thereby modulate some key post transcriptional processes such as splicing, translation, capping of mRNAs, and so on . Noncoding RNA Evf2 is reported to transcribe from an intergenic sequence between Dlx5/6, forming a complex with Dlx2 that increases the transcription of Dlx5/6.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA RP11-380D23.2 Drives Distal-Proximal Patterning of the Lung by Regulating PITX2 Expression

et al. 2017

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Early lung development is a tightly orchestrated process encompassing (a) formation of definitive endoderm, (b) anteriorization of definitive endoderm, followed by (c) specification and maturation of both proximal and distal lung precursors. Several reports detailing the interaction of genes and proteins during lung development are available; however, studies reporting the role(s) of long noncoding RNAs (lncRNA) in lung morphogenesis are limited. To investigate this, we tailored a protocol for differentiation of human-induced pluripotent stem cells into distal and proximal lung progenitors to mimic in vivo lung development. The authenticity of differentiated cells was confirmed by expression of key lung markers such as FoxA2, Sox-17, Nkx2.1, Pitx2, FoxJ1, CC10, SPC, and via scanning as well as transmission electron microscopy. We employed next generation sequencing to identify lncRNAs and categorized them based on their proximity to genes essential for lung morphogenesis. In-depth bioinformatical analysis of the sequencing data enabled identification of a novel lncRNA, RP11-380D23.2, which is located upstream of PITX2 and includes a binding site for PARP1. Chromatin immunoprecipitation and other relevant studies revealed that PARP1 is a repressor for PITX2. Whole genome microarray analysis of RP11-380D23.2/PITX2 knockdown populations of progenitors demonstrated enrichment in proximal progenitors and indicated altered distal-proximal patterning. Dysregulation of WNT effectors in both knockdowns highlighted direct modulation of PITX2 by RP11-380D23.2. Most of these results were validated in four independent hiPSC lines (including a patient-specific CFTR mutant line). Taken together, these findings offer a mechanistic explanation underpinning the role of RP11-380D23.2 during lung morphogenesis via WNT signaling. Stem Cells 2018;36:218-229.

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Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA RP11-380D23.2 Drives Distal-Proximal Patterning of the Lung by Regulating PITX2 Expression

et al. 2017

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“…Although lncRNAs are involved in a range of cellular processes, their major impact is in the regulation of gene expression patterns through their interactions with chromatin modifiers, DNA, RNA, and RNA-binding proteins (RBPs) (Bhat et al, 2016;Quinn & Chang, 2016). At the transcriptional level, lncRNAs affect chromatin organization, the formation of nuclear speckles, and RNA polymerase II activity (Bhat et al, 2016;Hutchinson et al, 2007;Pandey et al, 2008). At the posttranscriptional level, lncRNAs interact with various RNAs and proteins and thereby regulate splicing, mRNA turnover, and protein translation (Bhat et al, 2016;Dykes & Emanueli, 2017;Quinn & Chang, 2016;Rinn & Chang, 2012).…”

Section: Long Noncoding Rnas In Admentioning

confidence: 99%

“…At the transcriptional level, lncRNAs affect chromatin organization, the formation of nuclear speckles, and RNA polymerase II activity (Bhat et al, 2016;Hutchinson et al, 2007;Pandey et al, 2008). At the posttranscriptional level, lncRNAs interact with various RNAs and proteins and thereby regulate splicing, mRNA turnover, and protein translation (Bhat et al, 2016;Dykes & Emanueli, 2017;Quinn & Chang, 2016;Rinn & Chang, 2012). LncRNAs can also function as "decoys" for interacting molecules such as microRNAs and RBPs and thus influence their availability to other molecules, particularly mRNAs.…”

Section: Long Noncoding Rnas In Admentioning

confidence: 99%

Noncoding RNAs in Alzheimer's disease

et al. 2018

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia among the elderly worldwide. Despite intense efforts to develop drugs for preventing and treating AD, no effective therapies are available as yet, posing a growing burden at the personal, medical, and socioeconomic levels. AD is characterized by the production and aggregation of amyloid β (Aβ) peptides derived from amyloid precursor protein (APP), the presence of hyperphosphorylated microtubule-associated protein Tau (MAPT), and chronic inflammation leading to neuronal loss. Aβ accumulation and hyperphosphorylated Tau are responsible for the main histopathological features of AD, Aβ plaques, and neurofibrillary tangles (NFTs), respectively. However, the full spectrum of molecular factors that contribute to AD pathogenesis is not known. Noncoding (nc)RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), regulate gene expression at the transcriptional and posttranscriptional levels in various diseases, serving as biomarkers and potential therapeutic targets. There is rising recognition that ncRNAs have been implicated in both the onset and pathogenesis of AD. Here, we review the ncRNAs implicated posttranscriptionally in the main AD pathways and discuss the growing interest in targeting regulatory ncRNAs therapeutically to combat AD pathology. WIREs RNA 2018, 9:e1463. doi: 10.1002/wrna.1463 This article is categorized under: RNA in Disease and Development > RNA in Disease.

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“…More recently, specific type of lncRNAs like enhancer RNA (eRNA) have been reported to modulate target gene expression [6, 27]. Here we discuss several immune regulatory lncRNAs that modulate gene transcription through their unique mechanisms.…”

Section: Introductionmentioning

confidence: 99%

LncRNAs and immunity: watchdogs for host pathogen interactions

et al. 2017

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Immune responses combat various infectious agents by inducing inflammatory responses, antimicrobial pathways and adaptive immunity. The polygenic responses to these external stimuli are temporally and coordinately regulated. Specific lncRNAs are induced to modulate innate and adaptive immune responses which can function through various target interactions like RNA-DNA, RNA-RNA, and RNA-protein interaction and hence affect the immunogenic regulation at various stages of gene expression. LncRNA are found to be present in various immune cells like monocytes, macrophages, dendritic cells, neutrophils, T cells and B cells. They have been shown to be involved in many biological processes, including the regulation of the expression of genes, the dosage compensation and genomics imprinting, but the knowledge how lncRNAs are regulated and how they alter cell differentiation/function is still obscure. Further dysregulation of lncRNA has been seen in many diseases, but as yet very less research has been carried out to understand the role of lncRNAs in regulation during host-pathogens interactions. In this review, we summarize the functional developments and mechanism of action of lncRNAs, in immunity and defense of host against pathogens.

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Long non-coding RNAs: Mechanism of action and functional utility

Cited by 208 publications

References 113 publications

Long Noncoding RNA RP11-380D23.2 Drives Distal-Proximal Patterning of the Lung by Regulating PITX2 Expression

Long Noncoding RNA RP11-380D23.2 Drives Distal-Proximal Patterning of the Lung by Regulating PITX2 Expression

Noncoding RNAs in Alzheimer's disease

LncRNAs and immunity: watchdogs for host pathogen interactions

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