Distinct small non-coding RNA landscape in the axons and released extracellular vesicles of developing primary cortical neurons and the axoplasm of adult nerves

Mesquita-Ribeiro, Raquel; Fort, Rafael Sebastián; Rathbone, Alex; Farias, Joaquina; Lucci, Cristiano; James, Victoria; Sotelo-Silveira, Jose; Duhagon, Maria Ana; Dajas-Bailador, Federico

Abstract

Neurons have highlighted the needs for decentralized gene expression and specific RNA function in somato-dendritic and axonal compartments, as well as in intercellular communication via extracellular vesicles (EVs). Despite advances in miRNA biology, the identity and regulatory capacity of other small non-coding RNAs (sncRNAs) in neuronal models and local subdomains has been largely unexplored. We identified a highly complex and differentially localized content of sncRNAs in axons and EVs during early neuronal development of cortical primary neurons and in adult axons invivo. This content goes far beyond miRNAs and includes most known sncRNAs and precisely processed fragments from tRNAs, sno/snRNAs, Y RNAs and vtRNAs. Although miRNAs are the major sncRNA biotype in whole-cell samples, their relative abundance is significantly decreased in axons and neuronal EVs, where specific tRNA fragments (tRFs and tRHs/tiRNAs) mainly derived from tRNAs Gly-GCC, Val-CAC and Val-AAC predominate. Notably, although 5ʹ-tRHs compose the great majority of tRNA-derived fragments observed invitro, a shift to 3ʹ-tRNAs is observed in mature axons invivo. The existence of these complex sncRNA populations that are specific to distinct neuronal subdomains and selectively incorporated into EVs, equip neurons with key molecular tools for spatiotemporal functional control and cell-to-cell communication.

• Journal Article Type: Article
• Acceptance Date: Oct 29, 2021
• Online Publication Date: Dec 9, 2021
• Publication Date: 2021
• Deposit Date: Nov 8, 2021
• Publicly Available Date: Dec 10, 2022
• Journal: RNA Biology
• Print ISSN: 1547-6286
• Electronic ISSN: 1555-8584
• Peer Reviewed: Peer Reviewed
• Volume: 18
• Issue: sup2
• Pages: 832-855
• DOI: https://doi.org/10.1080/15476286.2021.2000792
• Keywords: Cell Biology; Molecular Biology
• Public URL: https://nottingham-repository.worktribe.com/output/6672877
• Publisher URL: https://www.tandfonline.com/doi/full/10.1080/15476286.2021.2000792
• Additional Information: This is an Accepted Manuscript of an article published by Taylor & Francis in RNA Biology on 9/12, available online: http://www.tandfonline.com/10.1080/15476286.2021.2000792