Biology subjects

Piwecka, M.

Publications and source records attributed to Piwecka, M..

4 recordsLinked to original sources

bioRxiv2025

Staufen2 modulates the temporal dynamics of human neurogenesis in vitro

RNA-binding proteins (RBPs) play a central role in post-transcriptional regulation during brain development, yet their specific functions in coordinating human neural lineage decisions remain poorly understood. Here, we investigate for the first time the role of the double-stranded RBP Staufen2 (STAU2) in human neurogenesis. Characterization of STAU2 knockout iPSC derived cells using scRNA-seq shows that loss of STAU2 disrupts neuroepithelial cell identity and accelerates neural differentiation by altering the activity of key transcription factors and driving early metabolic transitions. Additionally, STAU2 regulates the expression of miRNA host genes and alters miRNA-mediated post- transcriptional control in progenitor cells, which exerts additional effects on STAU2 regulated gene regulatory networks. These changes result in neural progenitor exhaustion, unstructured neural rosettes, and reduced organoid size. Together, our work uncovers a previously unrecognized role for STAU2 as a central regulator of early human neurogenesis, acting through both miRNA-mediated and transcriptional pathways to coordinate progenitor maintenance and neuronal fate specification.

molecular biology↗

bioRxiv2023

miR-7 controls glutamatergic transmission and neuronal connectivity in a Cdr1as-dependent manner

The circular RNA (circRNA) Cdr1as is conserved across mammals and highly expressed in neurons, where it directly interacts with microRNA miR-7. However, the biological function of this interaction is unknown. Here, using primary forebrain murine neurons, we demonstrate that stimulating neurons by sustained depolarization rapidly induced two-fold transcriptional up-regulation of Cdr1as and strong post-transcriptional stabilization of miR-7. Cdr1as loss caused doubling of glutamate release from stimulated synapses and increased frequency and duration of local neuronal bursts. Moreover, periodicity of neuronal networks was increased and synchronicity was impaired. Strikingly, these effects were reverted by sustained expression of miR-7 which also cleared Cdr1as molecules from neuronal projections. Consistently, without Cdr1as, transcriptomic changes caused by miR-7 overexpression were stronger (including miR-7-targets down-regulation) and enriched in secretion/synaptic plasticity pathways. Altogether, our results suggest that in forebrain neurons Cdr1as buffers miR-7 activity to control glutamatergic excitatory transmission and neuronal connectivity important for long-lasting synaptic adaptations.

molecular biology↗

bioRxiv2023

ciRS-7-miR7 regulate ischemia induced neuronal death via glutamatergic signaling

Brain functionality relies on finely tuned regulation of gene expression by networks of non-coding RNAs (ncRNAs) such as the one composed by the circular RNA ciRS-7 (also known as CDR1as), the microRNA miR-7 and the long non-coding RNA Cyrano. Here we describe ischemia induced alterations in the ncRNA network both in vitro and in vivo and in transgenic mice lacking ciRS-7 or miR-7. Our data show that cortical neurons downregulate ciRS-7 and Cyrano and upregulate miR-7 expression upon ischemic insults. Mice lacking ciRS-7 show reduced lesion size and motor impairment, whilst the absence of miR-7 alone leads to an increase in the ischemia induced neuronal death. Moreover, miR-7 levels in pyramidal excitatory neurons regulate dendrite morphology and glutamatergic signaling suggesting a potential molecular link to the in vivo phenotype. Our data reveal that ciRS-7 and miR-7 contribute to the outcome of ischemic stroke and shed new light into the pathophysiological roles of intracellular networks of non-coding RNAs in the brain.

molecular biology↗

bioRxiv2022

Analyses of circRNA expression throughout circadian rhythm reveal a strong link between Cdr1as and light-induced phase shifts in the SCN

Cdr1as is a conserved circular RNA (circRNA) enriched in the CNS and important for maintaining brain homeostasis. The loss of Cdr1as results in aberrant synaptic transmission and deregulation of stress response and circadian clock genes. However, it is not known whether the expression of Cdr1as or circRNAs, in general, follows a circadian pattern in different tissues. Here, using newly generated and public RNA-Seq data, we monitor circRNA expression throughout circadian rhythm in various mouse brain regions. We demonstrate that Cdr1as, despite its stable character, has a highly dynamic expression during the circadian cycle in the mouse suprachiasmatic nucleus (SCN). Cdr1as is one of the highest expressed RNAs in a cluster associated with light-induced synaptic transmission and phase shift in the SCN. Further, we identified that another brain enriched circRNA, mbl, is also substantially deregulated upon light induction in the fly head. Our study highlights the potential impact of abundant and conserved circRNAs on maintaining a healthy circadian cycle across species.

systems biology↗