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Publication : Distinct fingerprints of tRNA-derived small non-coding RNA in animal models of neurodegeneration.

First Author  Baindoor S Year  2024
Journal  Dis Model Mech Volume  17
Issue  11 PubMed ID  39552337
Mgi Jnum  J:376826 Mgi Id  MGI:7785724
Doi  10.1242/dmm.050870 Citation  Baindoor S, et al. (2024) Distinct fingerprints of tRNA-derived small non-coding RNA in animal models of neurodegeneration. Dis Model Mech 17(11)
abstractText  Transfer RNA-derived small RNAs (tsRNAs) - categorized as tRNA-derived fragments (tRFs), tRNA-derived stress-induced RNAs (tiRNAs) and internal tRF (itRF) - are small non-coding RNAs that participate in various cellular processes such as translation inhibition and responses to cellular stress. We here identified tsRNA profiles within susceptible tissues in animal models of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's disease (PD) to pinpoint disease-specific tsRNAs and those shared across neurodegenerative diseases. We performed small RNA sequencing in the SOD1G93A and TDP43A315T mouse models of ALS (spinal cord), the TauP301S model of FTD (hippocampus), and the parkin/POLG model of PD (substantia nigra). Bioinformatic analysis showed higher expression of 5' tiRNAs selectively in the two ALS models, lower expression of 3' tRFs in both the ALS and FTD mouse models, and lower expression of itRF Arg in the PD model. Experimental validation confirmed the expression of tsRNAs. Gene Ontology analysis of targets associated with validated 3' tRFs indicated functions in the regulation of synaptic and neuronal pathways. Our profiling of tsRNAs indicates disease-specific fingerprints in animal models of neurodegeneration, which require validation in human disease.
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