MiR‐205 is up‐regulated in islets of diabetes‐susceptible mice and targets the diabetes gene <i>Tcf7l2</i>

Ouni, Meriem; Gottmann, Pascal; Westholm, Efraim; Schwerbel, Kristin; Jähnert, Markus; Stadion, Mandy; Rittig, Kilian; Vogel, Heike; Schürmann, Annette

doi:10.1111/apha.13693

Cited by 8 publications

(11 citation statements)

References 53 publications

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“…Alternative microexons are further found in genes encoding for proteins involved in cell growth and proliferation (e.g., Ptk2, Gnas), or in the regulation of cell polarity and cell adhesion (e.g., Mpp7) (Supplementary Table S2). In order to clarify the molecular basis for the lower Srrm4 expression in NZO islets, we took advantage of our miRNome data from islets of the two mouse models [29] in combination with a computation framework for target prediction [30]. Thereby, we detected two microRNAs, miR-326-3p and miR-3547-3p, which are expressed at a significantly higher level in NZO than in B6-ob/ob islets (Figure 3C), and may target and silence Srrm4 expression.…”

Section: Differences In Splicing Of Microexons In Nzo and B6-ob/ob Isletsmentioning

confidence: 99%

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Enriched Alternative Splicing in Islets of Diabetes-Susceptible Mice

Wilhelmi

Neumann²,

Jähnert

et al. 2021

IJMS

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Dysfunctional islets of Langerhans are a hallmark of type 2 diabetes (T2D). We hypothesize that differences in islet gene expression alternative splicing which can contribute to altered protein function also participate in islet dysfunction. RNA sequencing (RNAseq) data from islets of obese diabetes-resistant and diabetes-susceptible mice were analyzed for alternative splicing and its putative genetic and epigenetic modulators. We focused on the expression levels of chromatin modifiers and SNPs in regulatory sequences. We identified alternative splicing events in islets of diabetes-susceptible mice amongst others in genes linked to insulin secretion, endocytosis or ubiquitin-mediated proteolysis pathways. The expression pattern of 54 histones and chromatin modifiers, which may modulate splicing, were markedly downregulated in islets of diabetic animals. Furthermore, diabetes-susceptible mice carry SNPs in RNA-binding protein motifs and in splice sites potentially responsible for alternative splicing events. They also exhibit a larger exon skipping rate, e.g., in the diabetes gene Abcc8, which might affect protein function. Expression of the neuronal splicing factor Srrm4 which mediates inclusion of microexons in mRNA transcripts was markedly lower in islets of diabetes-prone compared to diabetes-resistant mice, correlating with a preferential skipping of SRRM4 target exons. The repression of Srrm4 expression is presumably mediated via a higher expression of miR-326-3p and miR-3547-3p in islets of diabetic mice. Thus, our study suggests that an altered splicing pattern in islets of diabetes-susceptible mice may contribute to an elevated T2D risk.

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Section: Differences In Splicing Of Microexons In Nzo and B6-ob/ob Isletsmentioning

confidence: 99%

“…(C) Elevated expression of miR-326-3p and miR-3547-3p in islets of NZO. Data extracted from miRNA-seq data from [29]. * p < 0.05; ** p < 0.01; *** p < 0.001.…”

Section: Differences In Splicing Of Microexons In Nzo and B6-ob/ob Isletsmentioning

confidence: 99%

Enriched Alternative Splicing in Islets of Diabetes-Susceptible Mice

Wilhelmi

Neumann²,

Jähnert

et al. 2021

IJMS

Self Cite

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“…[17][18][19][20] Here, it is important to have a link between the published article and the stored data otherwise, it is difficult to find the stored data in the endless expanses of the World Wide Web. 21 When it comes to data availability, the longevity of the data supply should be considered. Data should be available as fast as possible, but also they should be available for a substantial time after their generation.…”

Section: Open Research Data -Expectations and Limitationsmentioning

confidence: 99%

“…The combination of a published article with primary data or additional information stored in data repositories is a good example of how to increase the availability of data to the public 17–20 . Here, it is important to have a link between the published article and the stored data otherwise, it is difficult to find the stored data in the endless expanses of the World Wide Web 21 . When it comes to data availability, the longevity of the data supply should be considered.…”

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confidence: 99%

Open research data – Expectations and limitations

Kirschner

2022

Acta Physiologica

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far, publications are the universal current for scientists. To gain rewards for the provision of open data could increase acceptance. One of the biggest concerns scientist raise against open data is how the ownership of these data is handled. Here, new technologies might help. The new developing techniques to link data sets with unique digital identifiers could provide a solution to this problem. CONFLICT OF INTERESTNo conflict of interest to declare.

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“…Mechanistically, miR-205-5p directly interacts with the Tcf7l2 gene, a transcription factor that regulates genes involved in Wnt signalling and beta-cell function. Other predicted targets for miR-205-5p include Plcb1, Nphp1 and Cxxc4, and Plcb1, whose expression is significantly downregulated in beta-cells when miR-205-5p is overexpressed (53).…”

Section: Mirnas Regulate Beta-cell Differentiationmentioning

confidence: 99%

miRNAs provide mechanisms for integrated control of endocrine pancreas homeostasis and metabolic disease pathogenesis: a narrative review

Du¹,

Vidal-Puig²,

Rodríguez‐Cuenca³

2022

ExRNA

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Background and Objective: microRNAs (miRNAs) are short non-coding RNAs that have emerged to be the novel post-transcriptional regulators of gene expression, contributing to the development of metabolic diseases such as diabetes. Also, new and more precise high-throughput analytical tools have made it possible to study miRNAs' complex causative roles and targets. Here, we summarise the available evidence for the roles of miRNAs in the endocrine pancreas regulating fundamental cellular processes in beta-cells and the pathology of diabetes.Methods: We searched PubMed for research conducted and published before June 2022 using classical Boolean expressions. Only manuscripts written in English were considered.Key Content and Findings: Numerous miRNAs in the endocrine pancreas have been reported to regulate the fundamental cellular processes in beta-cells, such as proliferation, differentiation, apoptosis, and insulin biosynthesis and secretion by post-transcriptionally repressing their targets, as well as contributing to the pathology of diabetes. Also, many miRNAs, as molecular cargo of exosomes-mediate the crosstalk between the pancreas and other peripheral organs, unravelling new pathophysiological mechanisms related to the onset and worsening of diabetes.Conclusions: This review summarised the existing evidence of the complex network of miRNAs regulating the endocrine pancreas function and pathology of diabetes, providing the theoretical base for a future scientific study revealing the mechanism of diabetes and facilitating the discovery of new therapeutical targets in clinical practise.

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MiR‐205 is up‐regulated in islets of diabetes‐susceptible mice and targets the diabetes gene Tcf7l2

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 8 publications

References 53 publications

Enriched Alternative Splicing in Islets of Diabetes-Susceptible Mice

Enriched Alternative Splicing in Islets of Diabetes-Susceptible Mice

Open research data – Expectations and limitations

miRNAs provide mechanisms for integrated control of endocrine pancreas homeostasis and metabolic disease pathogenesis: a narrative review

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