Genetic inactivation of Translin/Trax RNase disrupts miRNAs, hippocampal synaptic plasticity, and memory

Mahesh Shivarama Shetty; Junko Kasuya; Xiuping Fu; Marisol Carmela Lauffer; Satya Murthy Tadinada; Tania Chatterjee Chowdhury; Zeru Peterson; Knute D. Carter; Jay M Baraban; Ted Abel

doi:10.1016/j.isci.2026.116188

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Genetic inactivation of Translin/Trax RNase disrupts miRNAs, hippocampal synaptic plasticity, and memory

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Genetic inactivation of Translin/Trax RNase disrupts miRNAs, hippocampal synaptic plasticity, and memory

Mahesh Shivarama Shetty, Junko Kasuya, Xiuping Fu, Marisol Carmela Lauffer, Satya Murthy Tadinada, Tania Chatterjee Chowdhury, Zeru Peterson, Knute D. Carter, Jay M Baraban and Ted Abel

iScience, Vol.29(6), 116188

06/19/2026

DOI: 10.1016/j.isci.2026.116188

PMCID: PMC13266039

PMID: 42305625

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Abstract

Neurons utilize RNA interference in the reversible translational repression of synaptically localized mRNAs, enabling rapid translation in response to synaptic activity. Two evolutionarily conserved proteins, Translin and Trax, form an RNase complex that processes miRNAs, tRNAs, and siRNAs. To determine the specific role of the RNase activity of this complex in brain function, we employed a mouse line harboring a point mutation in Trax (E126A) that renders the Translin/Trax RNase inactive. At the molecular level, we found alterations in the levels of multiple small RNAs, including miRNAs, tsRNAs, and substantial downregulation of gene expression at the mRNA level in the hippocampus of TraxE126A mice. At the synaptic level, TraxE126A mice exhibit deficits in specific forms of long-term hippocampal synaptic plasticity. At the behavioral level, TraxE126A mice display impaired long-term spatial memory and altered open-field behavior. These studies reveal the functional role of Translin/Trax RNase in the mammalian brain. [Display omitted] •Evolutionarily conserved proteins, Translin and Trax, form an RNase complex•Mutant mice with RNase-dead complex show altered hippocampal miRNA levels•Mutant mice show impaired hippocampal gene expression, plasticity, and behavior•Translin/Trax RNase is an important regulator of miRNA-mediated gene expression Genetics; Molecular biology; Neuroscience; Omics

Genetics

Molecular Biology

Neuroscience

omics

Details

Title: Subtitle: Genetic inactivation of Translin/Trax RNase disrupts miRNAs, hippocampal synaptic plasticity, and memory
Creators: Mahesh Shivarama Shetty - University of Iowa
Junko Kasuya - University of Iowa
Xiuping Fu - Johns Hopkins University School of Medicine
Marisol Carmela Lauffer - University of Iowa
Satya Murthy Tadinada - University of Iowa
Tania Chatterjee Chowdhury - University of Iowa
Zeru Peterson - University of Iowa
Knute D. Carter - University of Iowa
Jay M Baraban - Johns Hopkins University School of Medicine
Ted Abel - Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, 51 Newton Rd, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: iScience, Vol.29(6), 116188
DOI: 10.1016/j.isci.2026.116188
PMID: 42305625
PMCID: PMC13266039
NLM abbreviation: iScience
ISSN: 2589-0042
eISSN: 2589-0042
Publisher: Elsevier Inc; CAMBRIDGE
Grant note: National Institutes of Health: R01 MH 087463 Roy J. Carver Charitable Trust
This work was supported by funding from the National Institutes of Health R01 MH 087463 to T.A. T.A. is also supported by the Roy J. Carver Charitable Trust.
Language: English
Date published: 06/19/2026
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Biostatistics; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9985174496502771

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