Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice

Papadopoulou, Aikaterini S.; Serneels, Lutgarde; Achsel, Tilmann; Mandemakers, Wim; Callaerts-Végh, Zsuzsanna; Dooley, James; Lau, Pierre; Ayoubi, Torik; Radælli, Enrico; Spinazzi, Marco; Neumann, Melanie; Hébert, Sébastien S.; Silahtaroglu, Asli; Liston, Adrian; D’Hooge, Rudi; Glatzel, Markus; Strooper, Bart De

doi:10.1016/j.nbd.2014.10.006

Cited by 48 publications

(52 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Restoring these brakes on the apoptotic pathway via overexpression of miR-29 or miR-24 could be an effective therapeutic strategy that promotes long-term neuroprotection. A previous study reported that mice partially deleted for miR-29 (deletion of the miR-29a/b1 loci) had grossly normal brains but exhibited an ataxic phenotype [42]. Our findings that apoptosis is not increased in miR-29 knockout neurons support the hypothesis that observed phenotypes in these studies are more likely to be due to the effect of miR-29 on neuronal function rather than survival.…”

Section: Discussionsupporting

confidence: 88%

Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes

et al. 2016

View full text Add to dashboard Cite

Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR-29 family of microRNAs (miRNAs) are induced with neuronal maturation and that overexpression of miR-29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR-29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR-29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR-29-deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR-24 as another miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR-29 by targeting a similar repertoire of pro-death BH3-only genes. These results reveal that mature neurons engage redundant brakes to restrict the apoptotic pathway and ensure their long-term survival.

show abstract

Section: Discussionsupporting

confidence: 88%

Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Medrano, Sequeira-Lopez & Gomez (2014) found an association of miR-143/145 cluster with hydronephrosis in mice. miR-29a/29b-1 cluster knockout mice developed ataxic features and cerebral alterations (Papadopoulou et al, 2015). It is becoming clear that miRNA clusters are important for maintaining normal function, responses to environmental stimuli and are involved with the development of pathological conditions.…”

Section: Mirna Clusters and Other Diseasesmentioning

confidence: 99%

“…Biological Reviews 93 (2018) 1955-1986 © 2018 Cambridge Philosophical Society Papadopoulou et al (2015) virus-mediated gene-delivery system for efficient knockdown of VEGF in vivo. Zhang et al (2012a) developed an artificial polycistronic miRNA construct consisting of two pre-miRNA backbones connected by a linker made of an antisense RNA sequence against the HIV-1 envelope (env) gene driven by a cytomegalovirus (CMV) promoter.…”

Section: Mirna In Therapymentioning

confidence: 99%

Clustered miRNAs and their role in biological functions and diseases

et al. 2018

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are endogenous, small non-coding RNAs known to regulate expression of protein-coding genes. A large proportion of miRNAs are highly conserved, localized as clusters in the genome, transcribed together from physically adjacent miRNAs and show similar expression profiles. Since a single miRNA can target multiple genes and miRNA clusters contain multiple miRNAs, it is important to understand their regulation, effects and various biological functions. Like protein-coding genes, miRNA clusters are also regulated by genetic and epigenetic events. These clusters can potentially regulate every aspect of cellular function including growth, proliferation, differentiation, development, metabolism, infection, immunity, cell death, organellar biogenesis, messenger signalling, DNA repair and self-renewal, among others. Dysregulation of miRNA clusters leading to altered biological functions is key to the pathogenesis of many diseases including carcinogenesis. Here, we review recent advances in miRNA cluster research and discuss their regulation and biological functions in pathological conditions.

show abstract

“…Mice lacking only the miR-29b/a-1 locus (therefore with residual miR-29 activity) reach adulthood, display ataxic phenotype and a mild loss of Purkinje cells in the cerebellum and die around 9 months of age (Papadopoulou et al, 2015). A similar cerebellar phenotype is induced acutely by miR-29 antagomiR (Roshan et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging

Ripa

Dolfi

Terrigno

et al. 2016

Preprint

View full text Add to dashboard Cite

Background: A widespread modulation of gene expression occurs in the aging brain, but little is known as to the upstream drivers of these changes. MicroRNAs emerged as fine regulators of gene expression in many biological contexts and they are modulated by age. MicroRNAs may therefore be part of the upstream drivers of the global gene expression modulation correlated with aging and aging-related phenotypes.

show abstract

Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice

Cited by 48 publications

References 101 publications

Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes

Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes

Clustered miRNAs and their role in biological functions and diseases

MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging

Contact Info

Product

Resources

About