Terminal nucleotidyltransferase Tent2 microRNA A-tailing enzyme regulates excitatory/inhibitory balance in the hippocampus
- Patrycja Wardaszka-Pianka1,
- Bozena Kuzniewska1,
- Natalia Guminska2,
- Anna Hojka-Osinska3,
- Monika Puchalska4,
- Jacek Milek1,
- Aleksandra Stawikowska1,
- Pawel Krawczyk2,
- Francois Philippe Pauzin5,
- Tomasz Wojtowicz6,
- Kasia Radwanska4,
- Clive Raymond Bramham5,
- Andrzej Dziembowski2 and
- Magdalena Dziembowska1,7
- 1 Department of Animal Physiology, Faculty of Biology, University of Warsaw, Poland;
- 2 Laboratory of RNA Biology, International Institute of Molecular and Cell Biology, Poland;
- 3 Bioinformatics Core Facility, International Institute of Molecular and Cell Biology, Poland;
- 4 Laboratory of Molecular Basis of Behavior, Nencki Institute of Experimental Biology, Poland;
- 5 Department of Biomedicine, University of Bergen, Norway;
- 6 Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Poland
- ↵* Corresponding author; email: m.dziembowska{at}uw.edu.pl
Abstract
One of the post-transcriptional mechanisms regulating the stability of RNA molecules involves the addition of non-templated nucleotides to their 3' ends, a process known as RNA tailing. To systematically investigate the physiological consequences of terminal nucleotidyltransferase TENT2 absence on RNA 3' end modifications in the mouse hippocampus, we developed a new Tent2 knockout mouse. Electrophysiological measurements revealed increased excitability in Tent2 KO hippocampal neurons, and behavioral analyses showed decreased anxiety and improved fear extinction in these mice. At the molecular level, we observed changes in miRNAs monoadenylation in Tent2 KO mouse hippocampus, but found no effect of the TENT2 loss on the mRNAs total poly(A) tail length, as measured by Direct Nanopore RNA sequencing. Moreover, differential expression analysis revealed transcripts related to synaptic transmission to be downregulated in the hippocampus of Tent2 knockout mice. These changes may explain the observed behavioral and electrophysiological alterations. Our data thus establishes a link between TENT2-dependent miRNA tailing and the balance of inhibitory and excitatory neurotransmission.
Keywords
- Received August 22, 2024.
- Accepted February 25, 2025.
- Published by Cold Spring Harbor Laboratory Press for the RNA Society
This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
