Oklahoma Study In 2023 Finds That Host Gene SNHG15 Aids SARS-CoV-2 Entry Via Oncogene RABL2A
Nikhil Prasad Fact checked by:Thailand Medical News Team Apr 16, 2024 1 week, 6 days, 7 hours ago
COVID-19 News: The ongoing COVID-19 pandemic caused by SARS-CoV-2 has underscored the critical need for understanding the molecular intricacies of viral entry into host cells. The virus employs a sophisticated mechanism involving its spike (S) protein, particularly the receptor-binding domain (RBD) within the S1 subunit, to interact with the angiotensin-converting enzyme 2 (ACE2) receptor on host cells. This interaction initiates a cascade of events leading to viral fusion and entry, ultimately culminating in infection. However, recent research has unveiled additional layers of complexity in this process, including the involvement of long noncoding RNAs (lncRNAs) such as small nucleolar RNA host gene 15 (SNHG15) and cellular proteins like Rab-like protein 2A (RABL2A) that is also an oncogene in modulating viral entry efficiency.
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Host Gene SNHG15 Aids SARS-CoV-2 Entry Via Protein RABL2A.
SNHG15 overexpression enhances SARS-CoV-2 entry into cells. (A) an experimental design schematic diagram. (B) Copy numbers of SNHG15, SNORA9 and RABL2A in HEK293T-ACE2 cells as determined by droplet digital PCR. (C-F) HEK293T – ACE2 cells were transfected with 100 ng of vector control (VC) or SNHG15 isoform 1overexpression plasmids (C, D) for 24 h, followed by infection with SARS-CoV-2 pseudovirus at the indicated doses for 72 h (E) on the X-axis or at a dose of 6 × 105 relative luciferase units (RLUs) for the indicated time points (F). The transfection efficiency of VC and SNHG15 overexpression plasmids is indicated by GFP (C). Scale bar: 100 µm. SNHG15 levels were determined by real-time PCR and were normalized to β-actin (D). Luciferase activity levels representing SARS-CoV-2 entry (Y-axis) were measured in the infected cells, and the results are expressed as RLUs (E, F).
The Emergence of SNHG15 as a Crucial Regulator
A pioneering study conducted at Oklahoma State University that is covered in this
COVID-19 News report has delved into the functional role of SNHG15 in SARS-CoV-2 entry. SNHG15, previously implicated in cancer pathogenesis, emerged as a key player in facilitating viral invasion. Through a series of meticulously designed experiments utilizing pseudotyped lentiviral particles bearing SARS-CoV-2 spike proteins, researchers elucidated SNHG15's impact on viral entry dynamics.
Investigating SNHG15's Effects on Viral Entry
The study utilized a SARS-CoV-2 pseudovirus system coupled with luciferase reporters to quantitatively assess viral entry efficiency. Overexpression of SNHG15 isoform 1 resulted in a significant increase in viral entry, as evidenced by elevated luciferase activity. Conversely, knockdown of SNHG15 using specific shRNAs led to a dose- and time-dependent reduction in viral entry, further highlighting the critical role of SNHG15 in mediating SARS-CoV-2 cellular invasion.
Unraveling the Molecular Interactions: SNHG15 and RABL2A
Furthe
r investigations delved into the molecular mechanisms underlying SNHG15-mediated enhancement of viral entry. RNA pulldown assays coupled with proteomics identified RABL2A, a member of the RAB GTPase family involved in endocytosis regulation, as a key interacting partner of SNHG15. Subsequent validation through RNA immunoprecipitation (RIP) assays confirmed the specific binding of SNHG15 to RABL2A, establishing a direct molecular link between these two entities.
Understanding RABL2A's Impact on SARS-CoV-2 Entry
RABL2A, known for its regulatory roles in intracellular trafficking pathways, emerged as a critical effector in SNHG15-mediated viral entry enhancement. Overexpression of RABL2A mirrored the effects observed with SNHG15 overexpression, leading to increased viral entry. Conversely, siRNA-mediated knockdown of RABL2A resulted in a dose- and time-dependent reduction in viral entry, further solidifying RABL2A's significance in modulating SARS-CoV-2 cellular invasion.
Implications and Future Directions
The elucidation of SNHG15 and RABL2A's roles in SARS-CoV-2 entry has far-reaching implications. Firstly, it underscores the multifaceted nature of viral entry mechanisms, highlighting the involvement of host factors beyond traditional receptor-ligand interactions. Secondly, it presents potential therapeutic avenues, with SNHG15 and RABL2A emerging as promising targets for the development of novel antiviral strategies. Future research endeavors may focus on unraveling the precise mechanisms underlying SNHG15-RABL2A interactions and exploring their therapeutic potential in combating COVID-19 and potentially other viral infections.
Conclusion: A Comprehensive Insight into Viral Entry Dynamics
In conclusion, Oklahoma State University's groundbreaking research has provided a comprehensive insight into the molecular intricacies of SARS-CoV-2 entry. The identification of SNHG15 and RABL2A as critical regulators of viral entry represents a significant advancement in our understanding of host-virus interactions. This knowledge not only contributes to the fundamental understanding of viral pathogenesis but also holds immense promise for the development of targeted interventions against COVID-19 and future emerging viral threats. As research in this field continues to evolve, we can anticipate novel therapeutic strategies that harness the intricate interplay between host factors and viral entry mechanisms to mitigate the impact of infectious diseases on global health.
The study findings were published in the peer reviewed journal: RNA Biology (Taylor & Francis).
https://www.tandfonline.com/doi/full/10.1080/15476286.2023.2241755
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