Enhanced packaging of U6 small nuclear RNA and splicing-related proteins into extracellular vesicles during HIV infection
Year: 2025
Type: article
Abstract: U6 small nuclear RNA (U6 snRNA), a critical spliceosome component primarily found in the nucleus, plays a vital role in RNA splicing. Our previous study, using the simian immunodeficiency virus (SIV) macaque model, revealed an increase of U6 snRNA in plasma extracellular vesicles (EVs) in acute retroviral infection. Given the limited understanding of U6 snRNA dynamics across cells and EVs, particularly in SIV infection, this research explores U6 snRNA trafficking and its association with splicing proteins in the nucleus, cytoplasm, and EVs. We observed a redistribution of U6 snRNA from the nucleus to EVs post-infection, accompanied by distinct protein profile changes and alterations in nucleic acid metabolism and spliceosome pathways. In addition, U6 machinery proteins changed in cells and EVs in a contrasting manner. The redistribution of U6 and related proteins we observed could be part of a viral strategy to redirect host splicing machinery, suggesting that U6 may have regulatory roles and be part of retroviral infection signature.
Source: Science Advances
Authors: Yiyao Huang, Ahmed Abdelgawad, Olesia Gololobova, Zhaohao Liao, Xinyu Cong, Mona Batish, Lei Zheng, Kenneth W. Witwer
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G1367552416, G168982208, Extracellular Vesicle-Mediated Immunomodulation in HIV Infection and Nicotine Abuse, Novel Approaches to Capture, Sorting, and Characterization of CNS-Origin Extracellular Vesicles, G5340997047, LSM880 Laser-scanning Microscope with Airyscan Module, Novel Separation Methods for exRNA Carriers: Extracellular Vesicles, Lipoprotein Particles, and Protein Aggregates, Extracellular Vesicle and Extracellular RNA Biomarkers of HIV-1 Central Nervous System Pathogenesis and Cigarette Use, The Johns Hopkins Center for AIDS Research (JHU CFAR), JHU Center for the Advancement of HIV Neurotherapeutics (JHU CAHN)
OpenAlex ID: W4408345613