Genetic inactivation of the Translin/Trax RNase activity alters small RNAs including miRNAs, disrupts gene expression and impairs distinct forms of hippocampal synaptic plasticity and memory

Mahesh Shivarama Shetty; Junko Kasuya; Xiuping Fu; Marisol Carmela Lauffer; Satya Murthy Tadinada; Tania Chatterjee Chowdhury; Jay Baraban; Ted Abel

doi:10.1101/2025.07.10.663777

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Genetic inactivation of the Translin/Trax RNase activity alters small RNAs including miRNAs, disrupts gene expression and impairs distinct forms of hippocampal synaptic plasticity and memory

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Genetic inactivation of the Translin/Trax RNase activity alters small RNAs including miRNAs, disrupts gene expression and impairs distinct forms of hippocampal synaptic plasticity and memory

Mahesh Shivarama Shetty, Junko Kasuya, Xiuping Fu, Marisol Carmela Lauffer, Satya Murthy Tadinada, Tania Chatterjee Chowdhury, Jay Baraban and Ted Abel

bioRxiv

Cold Spring Harbor Laboratory, 1.1

07/11/2025

DOI: 10.1101/2025.07.10.663777

PMCID: PMC12265517

PMID: 40672149

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https://doi.org/10.1101/2025.07.10.663777View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

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 which 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 and acoustic-startle behavior. These studies reveal the functional role of Translin/Trax RNase in the mammalian brain.

Neuroscience

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Title: Subtitle: Genetic inactivation of the Translin/Trax RNase activity alters small RNAs including miRNAs, disrupts gene expression and impairs distinct forms of hippocampal synaptic plasticity and memory
Creators: Mahesh Shivarama Shetty
Junko Kasuya
Xiuping Fu - Johns Hopkins University School of Medicine
Marisol Carmela Lauffer
Satya Murthy Tadinada
Tania Chatterjee Chowdhury - University of Iowa
Jay Baraban - Johns Hopkins University School of Medicine
Ted Abel
Resource Type: Preprint
Publication Details: bioRxiv
Edition: 1.1
DOI: 10.1101/2025.07.10.663777
PMID: 40672149
PMCID: PMC12265517
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 07/11/2025
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984847999502771

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