The landscape of miRNA editing in animals and its impact on miRNA biogenesis and targeting

Li, Lishi; Song, Yulong; Shi, Xuliang; Liu, Jianheng; Xiong, Shangkun; Chen, Wanying; Fu, Qiang; Huang, Zichao; Gu, Nannan; Zhang, Rui

doi:10.1101/gr.224386.117

Cited by 83 publications

(96 citation statements)

References 62 publications

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“…MicroRNA editing is a widespread phenomenon which also affects many vasoactive microRNAs, as demonstrated recently in a study by Li et al The authors mapped microRNA A-to-I editing at an unprecedented scale and found 2711 potential pri-miR editing sites within approximately 80% of all human pri-miRs [117]. MicroRNA editing profiles were also found to be tissue-specific, which is in agreement with previous findings [113,115,118].…”

Section: Microrna A-to-i Editing In Neovascularizationsupporting

confidence: 85%

An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

Kwast

Quax

Nossent

2019

Cells

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Therapeutic neovascularization can facilitate blood flow recovery in patients with ischemic cardiovascular disease, the leading cause of death worldwide. Neovascularization encompasses both angiogenesis, the sprouting of new capillaries from existing vessels, and arteriogenesis, the maturation of preexisting collateral arterioles into fully functional arteries. Both angiogenesis and arteriogenesis are highly multifactorial processes that require a multifactorial regulator to be stimulated simultaneously. MicroRNAs can regulate both angiogenesis and arteriogenesis due to their ability to modulate expression of many genes simultaneously. Recent studies have revealed that many microRNAs have variants with altered terminal sequences, known as isomiRs. Additionally, endogenous microRNAs have been identified that carry biochemically modified nucleotides, revealing a dynamic microRNA epitranscriptome. Both types of microRNA alterations were shown to be dynamically regulated in response to ischemia and are able to influence neovascularization by affecting the microRNA’s biogenesis, or even its silencing activity. Therefore, these novel regulatory layers influence microRNA functioning and could provide new opportunities to stimulate neovascularization. In this review we will highlight the formation and function of isomiRs and various forms of microRNA modifications, and discuss recent findings that demonstrate that both isomiRs and microRNA modifications directly affect neovascularization and vascular remodeling.

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Section: Microrna A-to-i Editing In Neovascularizationsupporting

confidence: 85%

An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

Kwast

Quax

Nossent

2019

Cells

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“…However, because editing of a primary microRNA affects the processing efficiency of the microRNA catalyzed by the double‐strand RNase enzymes, DROSHA and DICER, the editing level of primary microRNA is not always equal to the editing level of mature microRNA, which finally functions as the posttranscriptional regulator . A recent comprehensive analysis showed that the difference in the editing level between a primary microRNA and mature microRNA is >10% in approximately half of the microRNAs . An improved method to amplify mature microRNA was published in 2012 .…”

Section: Discussionmentioning

confidence: 99%

“…32,33 A recent comprehensive analysis showed that the difference in the editing level between a primary microRNA and mature microRNA is >10% in approximately half of the microRNAs. 34 An improved method to amplify mature microRNA was published in 2012. 28 which are contained in TaqMan Advanced miRNA Assays (Thermo Fisher Scientific).…”

Section: Discussionmentioning

confidence: 99%

Altered editing level of microRNAs is a potential biomarker in lung adenocarcinoma

et al. 2018

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Adenosine‐to‐inosine (A‐to‐I) microRNA editing is associated with tumor phenotypes in various cancer types. Recent analyses of The Cancer Genome Atlas (TCGA) dataset have shown several microRNAs that undergo A‐to‐I editing in human cancers, some of which have been reported to be associated with prognosis. Herein, we examined published small RNA deep sequencing data of 74 cases of lung adenocarcinoma (AD) and the corresponding normal counterpart (NC) specimen in silico in order to identify A‐to‐I microRNA editing events. Editing levels of miR‐379‐5p, miR‐99a‐5p, and miR‐497‐5p were lower in AD than in NC and, in a large number of cases, the editing level of miR‐200b‐3p was higher in AD than in NC. Difference in the editing level between AD and NC was largest for miR‐99a‐5p. Then, we examined the editing level of miR‐99a‐5p in 50 surgically resected lung adenocarcinoma cases at our institution by a conventional sequence‐based method, and its association with clinical outcomes. The editing level of miR‐99a‐5p was significantly lower in 19 cases of AD (38%) than in corresponding NC. These cases showed a shorter overall survival as assessed using the log‐rank test (P = .047). This trend was consistent with previous analyses of TCGA dataset. The altered editing level of microRNAs in lung adenocarcinoma could serve as a potential biomarker.

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“…First, ablation of ADARs in Caenorhabditis elegans and in mice was reported to compromise pri-or pre-miRNA processing, resulting in altered miRNA levels [57]. Second, in human cell lines (HEK293 cells), destabilization of miRNA structure by editing events on regions outside of seed sequences resulted in alterations of (i) miRNA processing by the DROSHA/DICER complex (e.g., miR-151, let7-g, miR-33, miR-133a2, miR-197, miR-203 and miR-379) [58,59], and (ii) miRNA strand-selection and loading onto AGO [60,61]. In addition, adenosine deamination was shown to introduce specific mismatches potentially recognized by inosine-specific RBPs with endonuclease activity such as Tudor staphylococcal nuclease (Tudor-SN) and endonuclease V (ENDOV) [62][63][64].…”

Section: Mirna Maturationmentioning

confidence: 99%

Deciphering miRNAs’ Action through miRNA Editing

Sousa

Gjorgjieva

Dolicka

et al. 2019

IJMS

608

343

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MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called "RNA editing" involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA's stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA's ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.

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The landscape of miRNA editing in animals and its impact on miRNA biogenesis and targeting

Cited by 83 publications

References 62 publications

An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

Altered editing level of microRNAs is a potential biomarker in lung adenocarcinoma

Deciphering miRNAs’ Action through miRNA Editing

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