The miR-26 family regulates neural differentiation-associated microRNAs and mRNAs by directly targeting REST

Sauer, Mark V.; Was, Nina; Ziegenhals, Thomas; Wang, Xiantao; Hafner, Markus; Becker, Matthias; Fischer, Utz

doi:10.1242/jcs.257535

Cited by 10 publications

(14 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…P16 INK4A expression has recently been shown to be elevated in senescent iPSC-derived NPCs ( Nicaise et al 2019 ). The frequency of NPCs in the differentiation paradigm used in this study peaks at day 10 ( Sauer et al 2021 ). Thus, we next asked if the frequency of P16 INK4A + NPCs was increased in day 10 Malat1KO cultures.…”

Section: Resultsmentioning

confidence: 99%

lncRNAMalat1and miR-26 cooperate in the regulation of neuronal progenitor cell proliferation and differentiation

Was

Sauer

Fischer

et al. 2022

RNA

Self Cite

View full text Add to dashboard Cite

Neurogenesis is a finely tuned process, which depends on the balanced execution of expression programs that regulate cellular differentiation and proliferation. Different molecular players ranging from transcription factors to chromatin modulators control these programs. Adding to the complexity, also non-coding (nc)RNAs take part in this process. Here we analyzed the function of the long non-coding (lnc)RNA Malat1 during neural embryonic stem cell (ESC) differentiation. We find that deletion of Malat1 leads to inhibition of proliferation of neural progenitor cells (NPCs). Interestingly, this co-insides with an increase in the expression of miR-26 family members miR-26a and miR-26b in differentiating ESCs. Inactivation of miR-26a/b rescues the proliferative phenotype of Malat1 knockout (KO) cells and leads to accelerated neuronal differentiation of compound Malat1KO/mir-26KO ESCs. Together our work identifies a so far unknown interaction between Malat1 and miR-26 in the regulation of NPC proliferation and neuronal differentiation.

show abstract

Section: Resultsmentioning

confidence: 99%

lncRNAMalat1and miR-26 cooperate in the regulation of neuronal progenitor cell proliferation and differentiation

Was

Sauer

Fischer

et al. 2022

RNA

Self Cite

View full text Add to dashboard Cite

show abstract

“…Results that show only combinatorial miRNA sponges were capable of rescuing REST target expression indicate that the combined actions of multiple REST independent miRNAs are required for the de-repression of REST targeting during neurodevelopment. Indeed, knock out studies of the miR-26 family, identified in this project, show a direct link to REST repression, and highlight the miRNAs necessity for REST repression and in turn neural development [55]. EHMT1 regulated miRNAs are not limited to KS; miR-140 and miR-142 have been found to be elevated in patients with Autism [56, 57], miR-26 has routinely shown to be involved with Schizophrenia patients [58, 59].…”

Section: Discussionmentioning

confidence: 99%

The interplay between miRNAs and chromatin regulators underpins premature differentiation within neurodevelopmental disorders (NDDs)

Wood,

Alsaqati,

Harwood

2023

Preprint

View full text Add to dashboard Cite

Neurodevelopmental disorders (NDDs), such as Schizophrenia, Autism and Intellectual disability (ID) possess a wide range of neurological and physiological phenotypes, often showing significant overlap. Epigenetic regulators, including miRNAs and chromatin modifiers, have long been proposed as a possible cause of the broad range of symptoms associated with NDDs. However, the inherent complexity within miRNA regulatory networks has made it challenging to identify the key miRNAs and their mRNA targets and how they lead to the molecular deficits seen in NDDs. Here we investigate a regulatory pathway that connects the epigenetic repressor EHMT1 to the miRNA network to control REST/NRSF protein expression and show that it controls the timing of neurodevelopment. By use of a novel strategy utilising multi-miR sponges we identify key miRNAs that regulate REST/NRSF in human induced pluripotent stem cells (iPSC) and demonstrate that they control unidirectional developmental progression from the pluripotent stage into early neurodevelopment and then neuronal differentiation. These results demonstrate a highly regulated interaction between epigenetic regulators and miRNAs that is crucial to control the timing neurodevelopment and impacts on the origins of NDDs.

show abstract

“…Indeed, activity of miR-203 and REST co-regulate gene expression related to neuronal activity [ 27 ]. Additionally, miR-26 and miR-132 have been reported to target REST and its complex by participating in networks by negative feedback loops in neural tissue and controlling neurogenesis [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Detection of features predictive of microRNA targets by integration of network data

Cihan

Andrade‐Navarro

2022

PLoS ONE

View full text Add to dashboard Cite

Gene activity is controlled by multiple molecular mechanisms, for instance through transcription factors or by microRNAs (miRNAs), among others. Established bioinformatics tools for the prediction of miRNA target genes face the challenge of ensuring accuracy, due to high false positive rates. Further, these tools present poor overlap. However, we demonstrated that it is possible to filter good predictions of miRNA targets from the bulk of all predictions by using information from the gene regulatory network. Here, we take advantage of this strategy that selects a large subset of predicted microRNA binding sites as more likely to possess less false-positives because of their over-representation in RE1 silencing transcription factor (REST)-regulated genes from the background of TargetScanHuman 7.2 predictions to identify useful features for the prediction of microRNA targets. These enriched miRNA families would have silencing activity for neural transcripts overlapping the repressive activity on neural genes of REST. We analyze properties of associated microRNA binding sites and contrast the outcome to the background. We found that the selected subset presents significant differences respect to the background: (i) lower GC-content in the vicinity of the predicted miRNA binding site, (ii) more target genes with multiple identical microRNA binding sites and (iii) a higher density of predicted microRNA binding sites close to the 3’ terminal end of the 3’-UTR. These results suggest that network selection of miRNA-mRNA pairs could provide useful features to improve microRNA target prediction.

show abstract

The miR-26 family regulates neural differentiation-associated microRNAs and mRNAs by directly targeting REST

Cited by 10 publications

References 43 publications

lncRNAMalat1and miR-26 cooperate in the regulation of neuronal progenitor cell proliferation and differentiation

lncRNAMalat1and miR-26 cooperate in the regulation of neuronal progenitor cell proliferation and differentiation

The interplay between miRNAs and chromatin regulators underpins premature differentiation within neurodevelopmental disorders (NDDs)

Detection of features predictive of microRNA targets by integration of network data

Contact Info

Product

Resources

About