CNS microRNA profiles: a database for cell type enriched microRNA expression across the mouse central nervous system

Abstract

microRNAs are short, noncoding RNAs that can regulate hundreds of targets and thus shape the expression landscape of a cell. Similar to mRNA, they often exhibit cell type enriched expression and serve to reinforce cellular identity. In tissue with high cellular complexity, such as the central nervous system (CNS), it is difficult to attribute microRNA changes to a particular cell type. To facilitate interpretation of microRNA studies in these tissues, we used previously generated data to develop a publicly accessible and user-friendly database to enable exploration of cell type enriched microRNA expression. We provide illustrations of how this database can be utilized as a reference as well as for hypothesis generation. First, we suggest a putative role for miR-21 in the microglial spinal injury response. Second, we highlight data indicating that differential microRNA expression, specifically miR-326, may in part explain regional differences in inflammatory cells. Finally, we show that miR-383 expression is enriched in cortical glutamatergic neurons, suggesting a unique role in these cells. These examples illustrate the database's utility in guiding research towards unstudied regulators in the CNS. This novel resource will aid future research into microRNA-based regulatory mechanisms responsible for cellular phenotypes within the CNS.

Altered White Matter and microRNA Expression in a Murine Model Related to Williams Syndrome Suggests That miR-34b/c Affects Brain Development via Ptpru and Dcx Modulation

“…These miRNAs are transcribed under the same promoter on chromosome 9 [ 94 , 96 , 127 , 131 , 132 , 133 , 134 , 135 ], and belong to the evolutionarily conserved miR-34 cluster, which is known to be involved in cell differentiation and migration [ 94 ]—processes that were disrupted in the cortices of P30 NexKO mice compared to controls [ 56 ]. Moreover, miR-34b/c seem to be primarily expressed in neocortical neurons [ 136 , 137 , 138 ], suggesting that the observed downregulation occurred mainly in neurons in the cortices of NexKO mice compared to controls.…”

Exosomal Proteins and miRNAs as Mediators of Amyotrophic Lateral Sclerosis

“…They function by binding to either the 3 -untranslated region (UTR) or open reading frame (ORF) region of target mRNAs to mediate post-transcriptional gene silencing (Bartel, 2004;Chen and Rajewsky, 2007). In fact, evidence suggests that aberrant miRNA expression alone is capable of reprogramming neuron cell identity (Selbach et al, 2008;Yoo et al, 2011;Pomper et al, 2020). Changes in miRNA levels are stimulated under stressful conditions such as hypoxia and have been detected to regulate key proteins involved in ALS pathogenesis (Hosaka et al, 2019).…”

Advances and Challenges in Understanding MicroRNA Function in Tauopathies: A Case Study of miR-132/212

“…Recent RNA deep-sequencing efforts have shown that ~50–100 miRNAs are expressed at moderate to high levels in the mouse and human brain ( 51 – 53 ). Several of these are enriched in neurons, glia, or other cell types ( 54 ). Given the diversity of tau pathologies, selecting a candidate miRNA, and biological model for functional studies is a daunting task.…”