Search bioRxiv⌕ Search

Biology subjects

Varrault, A.

Publications and source records attributed to Varrault, A..

2 recordsLinked to original sources

CRISPR Activation/Inhibition Experiments Reveal that Expression of Intronic MicroRNA miR-335 Depends on the Promoter Activity of its Host Gene Mest

MicroRNAs are small non-coding RNAs that act as rheostats to modulate gene expression during development, physiology, and disease. Approximately half of mammalian microRNAs are intronic. It is unknown whether intronic miRNA transcription depends on their host gene or a microRNA-specific promoter. Here, we show that CRISPR inhibition of host gene Mest downregulated hosted miR-335 in mouse embryonic stem cells and brain organoids. Reciprocally, CRISPR transactivation of Mest upregulated miR-335. By contrast, activation of miR-335 predicted promoter had no effect. Thus, intronic miR-335 expression depends on the promoter activity of its host gene. This approach could serve to map microRNA promoters.

genomics↗

The mGlu7 receptor provides protective effects against epileptogenesis and epileptic seizures

Finding new targets to control or reduce seizure activity is essential to improve the management of epileptic patients. We hypothesized that activation of the pre-synaptic and inhibitory metabotropic glutamate receptor type 7 (mGlu7) reduces spontaneous seizures. We tested LSP2-9166, a recently developed mGlu7/4 agonist with unprecedented potency on mGlu7 receptors, in two paradigms of epileptogenesis. In a model of chemically induced epileptogenesis (pentylenetetrazol systemic injection), LSP2-9166 induces an antiepileptogenic effect rarely observed in preclinical studies. In particular, we found a bidirectional modulation of seizure progression by mGlu4 and mGlu7 receptors, the latter preventing kindling. In the intra-hippocampal injection of kainic acid mouse model that mimics the human mesial temporal lobe epilepsy, we found LSP2-9166 reduced seizure frequency and hippocampal sclerosis. LSP2-9166 also acts as an anti epileptic drug on established seizures in both models tested. Specific modulation of the mGlu7 receptor could represent a novel approach to reduce pathological network remodeling.

neuroscience↗