Systematic characterization of seed overlap microRNA cotargeting associated with lupus pathogenesis

Kitai, Hiroki; Kato, Noritoshi; Ogami, Koichi; Komatsu, Shintaro; Watanabe, Yu; Yoshino, Seiko; Koshi, Eri; Tsubota, Shoma; Funahashi, Yasuyuki; Maeda, Takahiro; Furuhashi, Kazuhiro; Ishimoto, Takuji; Kosugi, Tomoki; Maruyama, Shoichi; Kadomatsu, Kenji; Suzuki, Hiroshi

doi:10.1186/s12915-022-01447-4

Cited by 13 publications

(10 citation statements)

References 72 publications

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Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

“…In addition, we recently reported the systematic characterization of another type of miRNA cotargeting, "seed overlap" miRNA cotargeting (Figure 4b) [100]. We previously reported that downregulation of two miRNAs, miR-128 and miR-148a, additively alters their target KLF4 via extensive overlapping of target sites, leading to enhancement of the inflammatory responses in plasmacytoid dendritic cells in the systemic lupus erythematosus (SLE) mouse model [100]. Although conserved "seed overlap" sites cannot be bound by two miRNAs simultaneously, in contrast to two closely spaced target sites, conserved "seed overlap" sites increase susceptibility to overall downregulation by two distinct miRNAs through additive recruitment of two miRNAs to these sites at the transcriptome level.…”

Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

“…Thus, the association of miRNA cotargeting with miRNA cluster genes, distribution at multiple genomic loci, and a high probability of haplo-insufficient genes suggests that fine-tuning the "dosage" of both miRNAs and target mRNAs is important for the network regulation of miRNA target genes [100]. In addition, we recently reported the systematic characterization of another type of miRNA cotargeting, "seed overlap" miRNA cotargeting (Figure 4b) [100]. We previously reported that downregulation of two miRNAs, miR-128 and miR-148a, additively alters their target KLF4 via extensive overlapping of target sites, leading to enhancement of the inflammatory responses in plasmacytoid dendritic cells in the systemic lupus erythematosus (SLE) mouse model [100].…”

Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

“…Systematic characterization of target sites further revealed unique evolutionary features of miRNA target sites. Highly conserved target sites of broadly conserved miRNAs are largely divided into two classes-those conserved among eutherian mammals and from humans to Coelacanth-and the latter, including KLF4-cotargeting sites, has a stronger association with both "seed overlap" and "neighborhood" miRNA cotargeting [100]. In addition, a deeply conserved miRNA target class has a higher probability of haplo-insufficient genes.…”

Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

“…In addition, a deeply conserved miRNA target class has a higher probability of haplo-insufficient genes. Thus, the association of miRNA cotargeting with miRNA cluster genes, distribution at multiple genomic loci, and a high probability of haplo-insufficient genes suggests that fine-tuning the "dosage" of both miRNAs and target mRNAs is important for the network regulation of miRNA target genes [100].…”

Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

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Network Regulation of microRNA Biogenesis and Target Interaction

Komatsu

Kitai

Suzuki

2023

Cells

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MicroRNAs (miRNAs) are versatile, post-transcriptional regulators of gene expression. Canonical miRNAs are generated through the two-step DROSHA- and DICER-mediated processing of primary miRNA (pri-miRNA) transcripts with optimal or suboptimal features for DROSHA and DICER cleavage and loading into Argonaute (AGO) proteins, whereas multiple hairpin-structured RNAs are encoded in the genome and could be a source of non-canonical miRNAs. Recent advances in miRNA biogenesis research have revealed details of the structural basis of miRNA processing and cluster assistance mechanisms that facilitate the processing of suboptimal hairpins encoded together with optimal hairpins in polycistronic pri-miRNAs. In addition, a deeper investigation of miRNA–target interaction has provided insights into the complexity of target recognition with distinct outcomes, including target-mediated miRNA degradation (TDMD) and cooperation in target regulation by multiple miRNAs. Therefore, the coordinated or network regulation of both miRNA biogenesis and miRNA–target interaction is prevalent in miRNA biology. Alongside recent advances in the mechanistic investigation of miRNA functions, this review summarizes recent findings regarding the ordered regulation of miRNA biogenesis and miRNA–target interaction.

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Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

Section: Significance Of Mirna Cotargetingmentioning

confidence: 99%

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Network Regulation of microRNA Biogenesis and Target Interaction

Komatsu

Kitai

Suzuki

2023

Cells

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Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

Nag,

Mitra,

Tripathi

et al. 2023

Immunity Inflam & Disease

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BackgroundAutoimmune diseases (AD) are severe pathophysiological ailments that are stimulated by an exaggerated immunogenic response towards self‐antigens, which can cause systemic or site‐specific organ damage. An array of complex genetic and epigenetic facets majorly contributes to the progression of AD, thus providing significant insight into the regulatory mechanism of microRNA (miRNA). miRNAs are short, non‐coding RNAs that have been identified as essential contributors to the post‐transcriptional regulation of host genome expression and as crucial regulators of a myriad of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development.AimsThis article tends to deliberate and conceptualize the brief pathogenesis and pertinent epigenetic regulatory mechanism as well as miRNA networks majorly affecting five different ADs namely rheumatoid arthritis (RA), type 1 diabetes, multiple sclerosis (MS), systemic lupus erythematosus (SLE) and inflammatory bowel disorder (IBD) thereby providing novel miRNA‐based theranostic interventions.Results & DiscussionPertaining to the differential expression of miRNA attributed in target tissues and cellular bodies of innate and adaptive immunity, a paradigm of scientific expeditions suggests an optimistic correlation between immunogenic dysfunction and miRNA alterations.ConclusionTherefore, it is not astonishing that dysregulations in miRNA expression patterns are now recognized in a wide spectrum of disorders, establishing themselves as potential biomarkers and therapeutic targets. Owing to its theranostic potencies, miRNA targets have been widely utilized in the development of biosensors and other therapeutic molecules originating from the same.

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Molecular profiling and therapeutic tailoring to address disease heterogeneity in systemic lupus erythematosus

Karmakar,

Kumar,

Prabhu

et al. 2024

Clin Exp Med

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Systemic lupus erythematosus (SLE) is a chronic, heterogeneous, systemic autoimmune disease characterized by autoantibody production, complement activation, and immune complex deposition. SLE predominantly affects young, middle-aged, and child-bearing women with episodes of flare-up and remission, although it affects males at a much lower frequency (female: male; 7:1 to 15:1). Technological and molecular advancements have helped in patient stratification and improved patient prognosis, morbidity, and treatment regimens overall, impacting quality of life. Despite several attempts to comprehend the pathogenesis of SLE, knowledge about the precise molecular mechanisms underlying this disease is still lacking. The current treatment options for SLE are pragmatic and aim to develop composite biomarkers for daily practice, which necessitates the robust development of novel treatment strategies and drugs targeting specific responsive pathways. In this communication, we review and aim to explore emerging therapeutic modalities, including multiomics-based approaches, rational drug design, and CAR-T-cell-based immunotherapy, for the management of SLE.

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Systematic characterization of seed overlap microRNA cotargeting associated with lupus pathogenesis

Cited by 13 publications

References 72 publications

Network Regulation of microRNA Biogenesis and Target Interaction

Network Regulation of microRNA Biogenesis and Target Interaction

Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

Molecular profiling and therapeutic tailoring to address disease heterogeneity in systemic lupus erythematosus

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