Alanine tRNA fragments interacting with MEG3 long splice variant show tissue-, cellular compartment- and disease severity-dependent changes in Parkinson’s diseaseDownload PDF Download PDF ArticleOpen accessPublished: 22 August 2026Tamara Zorbaz1,2,Estelle R. Bennett1,2,Shani Vaknine Treidel1,2,Nimrod Madrer1,2,Arbel Zeira2,David S. Greenberg1,2,Iddo Paldor2,3 &…Hermona Soreq1,2 npj Parkinson's Disease (2026) Cite this articleSave articleView saved research We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.AbstractLong non-coding RNAs (lncRNAs) and tRNA fragments (tRFs) have emerged as important regulators in Parkinson’s disease (PD), but much remains unknown regarding their interactions. We report here that the long splice variant of MEG3 lncRNA interacts with alanine tRNA 3’-end fragments (3’-tRFs-Ala), and that both showed dysregulated levels in the substantia nigra of PD patients. Additionally, carriers of PD-risk mutations (LRRK2+, GBA+, SNCA+) had decreased levels of 3’-tRFs-Ala in their blood, and in GBA+ PD patients, reduced levels correlated with the severity of autonomic and sensory non-motor impairments. Paraquat-induced oxidative stress in neuroblastoma cells decreased 3’-tRFs-Ala levels in the nucleus but increased them in the cytoplasm, highlighting acute changes in subcellular localization. Simultaneously, 3’-tRFs-Ala bind nuclear spliceosome and cytoplasmic aminoacyl-tRNA synthetase proteins, suggesting an additional level of post-transcriptional regulation in neuronal and peripheral immune cells. Overall, the interacting MEG3 long splice variant and 3’-tRFs-Ala emerged as non-coding RNAs with dynamic and spatiotemporal roles in PD pathology.SubjectsCell biologyDiseasesGeneticsMolecular biologyNeurologyNeuroscienceAcknowledgementsThis study was supported by the Israel Science Foundation grant nos. 835/23, the Michael J. Fox Foundation grant 11183, and the ERA-NET NEURON_RV-025 B3phrenia project to H.S., and by the Shaare Zedek Medical Center and Hebrew University of Jerusalem joint grant to I.P. and H.S. We further acknowledge ELSC Postdoctoral fellowship, ELSC Peter Briess fellowship, and Ministry of Foreign Affairs Scholarship to T.Z., as well as Ken Stein and Keter Holdings support to H.S. Patient brain tissues were obtained from the NIH NeuroBioBank and Netherlands Brain Bank. Blood samples were collected at the Shaare Zedek Medical Center under a joint grant support to I.P. and H.S., and RNA-Seq data were gratefully obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/access-dataspecimens/download-data), RRID:SCR 006431 (For up-to-date information on the study visit www.ppmi-info.org). BioRender and ServierMedicalArt were used for parts of figures.Author informationAuthors and AffiliationsThe Edmond and Lily Safra Center of Brain Science, The Hebrew University of Jerusalem, Jerusalem, IsraelTamara Zorbaz, Estelle R. Bennett, Shani Vaknine Treidel, Nimrod Madrer, David S. Greenberg & Hermona SoreqDepartment of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelTamara Zorbaz, Estelle R. Bennett, Shani Vaknine Treidel, Nimrod Madrer, Arbel Zeira, David S. Greenberg, Iddo Paldor & Hermona SoreqThe Neurosurgery department, Shaare Zedek Medical center, Jerusalem, IsraelIddo PaldorAuthorsTamara ZorbazView author publicationsSearch author on:PubMed Google ScholarEstelle R. BennettView author publicationsSearch author on:PubMed Google ScholarShani Vaknine TreidelView author publicationsSearch author on:PubMed Google ScholarNimrod MadrerView author publicationsSearch author on:PubMed Google ScholarArbel ZeiraView author publicationsSearch author on:PubMed Google ScholarDavid S. GreenbergView author publicationsSearch author on:PubMed Google ScholarIddo PaldorView author publicationsSearch author on:PubMed Google ScholarHermona SoreqView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to Hermona Soreq.Ethics declarationsCompeting interestsThe authors declare no competing interests.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationRights and permissionsOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsAbout this articleDownload PDF