Emerging roles of DROSHA beyond primary microRNA processing

Lee, Dong Hoon; Shin, Chanseok

doi:10.1080/15476286.2017.1405210

Cited by 51 publications

(40 citation statements)

References 102 publications

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“…Accumulating evidence suggests that Drosha and Dicer can function beyond biogenesis of siRNAs/miRNAs (156). For example, Drosha has been shown to regulate mRNA stability and processing of a select group of RNAs (157). Dicer was shown to process the Huntingtin mRNA when the CAG repeat sequence expands and forms a stable duplex hairpin (158).…”

Section: Rna Interference Pathwaymentioning

confidence: 99%

Double-Stranded RNA Sensors and Modulators in Innate Immunity

Hur

2019

Annu. Rev. Immunol.

306

286

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Detection of double-stranded RNAs (dsRNAs) is a central mechanism of innate immune defense in many organisms. We here discuss several families of dsRNA-binding proteins involved in mammalian antiviral innate immunity. These include RIG-I-like receptors, protein kinase R, oligoadenylate synthases, adenosine deaminases acting on RNA, RNA interference systems, and other proteins containing dsRNA-binding domains and helicase domains. Studies suggest that their functions are highly interdependent and that their interdependence could offer keys to understanding the complex regulatory mechanisms for cellular dsRNA homeostasis and antiviral immunity. This review aims to highlight their interconnectivity, as well as their commonalities and differences in their dsRNA recognition mechanisms. KeywordsdsRNA; RIG-I-like receptor; protein kinase R; oligoadenylate synthase; dsRNA-dependent adenosine deaminase; RNA interference HHS Public Access

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Section: Rna Interference Pathwaymentioning

confidence: 99%

Double-Stranded RNA Sensors and Modulators in Innate Immunity

Hur

2019

Annu. Rev. Immunol.

306

286

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“…DGCR8 is a cofactor of Drosha, which interacts with and stabilises Drosha through its C‐terminal tail domain and its double‐stranded RNA (dsRNA)‐binding domains . However, according to recent reports , the functions of Drosha and DGCR8 may not be limited to pri‐miRNA processing (Fig. ).…”

Section: Various Roles Of Drosha and Dgcr8mentioning

confidence: 99%

Noncanonical functions of microRNA pathway enzymes – Drosha, DGCR8, Dicer and Ago proteins

2018

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MicroRNAs (miRNAs) are small regulatory noncoding RNAs that are generated in the canonical RNA interference (RNAi) pathway. Drosha, DiGeorge syndrome critical region 8 (DGCR8) and Dicer are key players in miRNA biogenesis. Argonaute (Ago) proteins bind to miRNAs and are guided by them to find messenger RNA targets and carry out post-transcriptional silencing of protein-coding genes. Recently, emerging evidence suggests that RNAi factors have a range of noncanonical functions that are beyond miRNA biogenesis. These functions pertain to various biological processes, such as development, transcriptional regulation, RNA processing and maintenance of genome integrity. Here, we review recent literature reporting miRNA-independent, noncanonical functions of Drosha, DGCR8, Dicer and Ago proteins and discuss the importance of these functions.

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“…In addition to its involvement in micro-RNA biogenesis, recent studies have also revealed its role outside of micro-RNA processing. These include regulating mRNA stability, transcriptional activation, RNA splicing, transcriptional termination of long noncoding RNAs that serve as primary micro-RNAs, maintenance of genome integrity and antiviral defense [27]. Importantly, Drosha has been observed to be involved in adult neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

Chronic social stress induces DNA methylation changes at an evolutionary conserved intergenic region in chromosome X

Hing

Braun

Cordner³

et al. 2018

Epigenetics

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Chronic stress resulting from prolonged exposure to negative life events increases the risk of mood and anxiety disorders. Although chronic stress can change gene expression relevant for behavior, molecular regulators of this change have not been fully determined. One process that could play a role is DNA methylation, an epigenetic process whereby a methyl group is added onto nucleotides, predominantly cytosine in the CpG context, and which can be induced by chronic stress. It is unknown to what extent chronic social defeat, a model of human social stress, influences DNA methylation patterns across the genome. Our study addressed this question by using a targeted-capture approach called Methyl-Seq to investigate DNA methylation patterns of the dentate gyrus at putative regulatory regions across the mouse genome from mice exposed to 14 days of social defeat. Findings were replicated in independent cohorts by bisulfite-pyrosequencing. Two differentially methylated regions (DMRs) were identified. One DMR was located at intron 9 of Drosha, and it showed reduced methylation in stressed mice. This observation replicated in one of two independent cohorts. A second DMR was identified at an intergenic region of chromosome X, and methylation in this region was increased in stressed mice. This methylation difference replicated in two independent cohorts and in Major Depressive Disorder (MDD) postmortem brains. These results highlight a region not previously known to be differentially methylated by chronic social defeat stress and which may be involved in MDD.

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Emerging roles of DROSHA beyond primary microRNA processing

Cited by 51 publications

References 102 publications

Double-Stranded RNA Sensors and Modulators in Innate Immunity

Double-Stranded RNA Sensors and Modulators in Innate Immunity

Noncanonical functions of microRNA pathway enzymes – Drosha, DGCR8, Dicer and Ago proteins

Chronic social stress induces DNA methylation changes at an evolutionary conserved intergenic region in chromosome X

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