Human disease-associated single nucleotide polymorphism changes the orientation of DROSHA on pri-mir-146a

Le, Cong Truc; Nguyễn, Thùy Linh; Nguyễn, Tùng Lâm; Nguyen, Tuan Anh

doi:10.1261/rna.077487.120

Cited by 13 publications

(7 citation statements)

References 46 publications

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“…Our findings in previous [ 19 ] and current studies not only explain the functions of these BMW elements in pri-miRNA processing, but also provide a foundation for interpreting the effects of any events, such as SNPs, somatic mutations and RNA-editing or modifications, which add or remove these BMW elements in pri-miRNAs, on miRNA biogenesis. We recently found that the diseases-related SNP (rs2910164) in pri-mir-146a creates a non-canonical mGHG motif at the apical junction and thus enhances the unproductive cleavage of DROSHA [ 26 ]. By performing pri-miRNA processing assays, we explain fundamental mechanisms of how this SNP alters miRNA biogenesis.…”

Section: Discussionmentioning

confidence: 99%

Bulges control pri-miRNA processing in a position and strand-dependent manner

Nguyễn

et al. 2020

RNA Biology

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MicroRNAs (miRNAs) play critical roles in gene expression and numerous human diseases. The success of miRNA biogenesis is largely determined by the primary miRNA (pri-miRNA) processing by the DROSHA-DGCR8 complex, called Microprocessor. Here, we analysed the high-throughput pri-miRNA processing assays and secondary structures of pri-miRNAs to investigate the roles of bulges in the pri-miRNA processing. We found that bulges in multiple places control both the cleavage efficiency and accuracy of pri-miRNA processing. These bulges were shown to act on Microprocessor via its catalytic subunit, DROSHA, and function in a position and strand-dependent manner. Interestingly, we discovered that the enriched and conserved bulges, called midB, can correct DROSHA orientation on pri-miRNAs, thereby enhancing production of miRNAs. The revealed functions of the bulges help improve our understanding of pri-miRNA processing and suggest their potential roles in miRNA biogenesis regulation.

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Section: Discussionmentioning

confidence: 99%

Bulges control pri-miRNA processing in a position and strand-dependent manner

Nguyễn

et al. 2020

RNA Biology

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“…SNVs in the key protein-coding genes are usually associated with health and disease in humans [ 9 , 10 ] and with economically important traits in domestic animals [ 11 , 12 ] through altering the regulation and/or function of these genes. Although—compared with protein-coding genes—the miRNA sequence is shorter (pre-miRNAs are only about 80 bp in length) and there are less SNVs, their SNVs have also been shown to be involved in multiple important traits in humans and domestic animals through altering the expression and functions of target genes by influencing the biogenesis [ 13 ], transcription [ 14 ], and target specificity [ 15 ] of miRNAs. rs2291418 in pre-miR-1229, for instance, is a causal SNV for Alzheimer’s disease (AD) through the control of miR-1229-3p biogenesis and the repression of the translation of its direct target, SORL1 , which encodes an AD-associated protein in the human brain [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

A Mutation in Endogenous saRNA miR-23a Influences Granulosa Cells Response to Oxidative Stress

Wang

Zeng

et al. 2022

Antioxidants

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Phenotypes are the result of the interaction between the gene and the environment, so the response of individuals with different genotypes to an environment is variable. Here, we reported that a mutation in miR-23a influences granulosa cells (GCs) response to oxidative stress, a common mechanism of environmental factors affecting female reproduction. We showed that nuclear miR-23a is a pro-apoptotic miRNA in porcine GCs through the activation of the transcription and function of NORHA, a long non-coding RNA (lncRNA) induces GC apoptosis and responses to oxidative stress. Mechanistically, miR-23a acts as an endogenous small activating RNA (saRNA) to alter histone modifications of the NORHA promoter through the direct binding to its core promoter. A C > T mutation was identified at −398 nt of the miR-23a core promoter, which created a novel binding site for the transcription factor SMAD4 and recruited the transcription repressor SMAD4 to inhibit miR-23a transcription and function in GCs. Notably, g.−398C > T mutation in the miR-23a promoter reduced GCs response to oxidative stress. In addition, g.−398C > T mutation was significantly associated with sow fertility traits. In short, our findings preliminarily revealed the genetic basis of individual differences in the response to oxidative stress from the perspective of a single mutation and identified miR-23a as a candidate gene for the environmental adaptation to oxidative stress.

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“…SNP in miRNA coding sequence (including pri-miRNA, pre-miRNA, and mature miRNA) can change miRNA processing, expression, or regulatory activity, thus leading to cancer. Le et al [ 23 ] found that SNP in the pri-mir-146a sequence could affect the expression of miR-146a. This SNP could induce a new mGHG sequence at the apical junction of pri-mir-146a to interact with the double-stranded RNA-binding domain of DROSHA.…”

Section: Microrna Genomic Variationmentioning

confidence: 99%

Mechanisms Controlling MicroRNA Expression in Tumor

Chen

Wang

et al. 2022

Cells

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MicroRNAs (miRNAs) are widely present in many organisms and regulate the expression of genes in various biological processes such as cell differentiation, metabolism, and development. Numerous studies have shown that miRNAs are abnormally expressed in tumor tissues and are closely associated with tumorigenesis. MiRNA-based cancer gene therapy has consistently shown promising anti-tumor effects and is recognized as a new field in cancer treatment. So far, some clinical trials involving the treatment of malignancies have been carried out; however, studies of miRNA-based cancer gene therapy are still proceeding slowly. Therefore, furthering our understanding of the regulatory mechanisms of miRNA can bring substantial benefits to the development of miRNA-based gene therapy or other combination therapies and the clinical outcome of patients with cancer. Recent studies have revealed that the aberrant expression of miRNA in tumors is associated with promoter sequence mutation, epigenetic alteration, aberrant RNA modification, etc., showing the complexity of aberrant expression mechanisms of miRNA in tumors. In this paper, we systematically summarized the regulation mechanisms of miRNA expression in tumors, with the aim of providing assistance in the subsequent elucidation of the role of miRNA in tumorigenesis and the development of new strategies for tumor prevention and treatment.

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Human disease-associated single nucleotide polymorphism changes the orientation of DROSHA on pri-mir-146a

Cited by 13 publications

References 46 publications

Bulges control pri-miRNA processing in a position and strand-dependent manner

Bulges control pri-miRNA processing in a position and strand-dependent manner

A Mutation in Endogenous saRNA miR-23a Influences Granulosa Cells Response to Oxidative Stress

Mechanisms Controlling MicroRNA Expression in Tumor

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