Tripathi, SK and Aneja, A and Borgaonkar, T and Das, S (2024) PSPC1 Binds to HCV IRES and Prevents Ribosomal Protein S5 Binding, Inhibiting Viral RNA Translation. In: Viruses, 16 (5).
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Abstract
Hepatitis C virus (HCV) infects the human liver, and its chronic infection is one of the major causes of Hepatocellular carcinoma. Translation of HCV RNA is mediated by an Internal Ribosome Entry Site (IRES) element located in the 5�UTR of viral RNA. Several RNA Binding proteins of the host interact with the HCV IRES and modulate its function. Here, we demonstrate that PSPC1 (Paraspeckle Component 1), an essential paraspeckle component, upon HCV infection is relocalized and interacts with HCV IRES to prevent viral RNA translation. Competition UV-crosslinking experiments showed that PSPC1 interacts explicitly with the SLIV region of the HCV IRES, which is known to play a vital role in ribosomal loading to the HCV IRES via interaction with Ribosomal protein S5 (RPS5). Partial silencing of PSPC1 increased viral RNA translation and, consequently, HCV replication, suggesting a negative regulation by PSPC1. Interestingly, the silencing of PSPC1 protein leads to an increased interaction of RPS5 at the SLIV region, leading to an overall increase in the viral RNA in polysomes. Overall, our results showed how the host counters viral infection by relocalizing nuclear protein to the cytoplasm as a survival strategy. © 2024 by the authors.
| Item Type: | Journal Article |
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| Publication: | Viruses |
| Publisher: | Multidisciplinary Digital Publishing Institute (MDPI) |
| Additional Information: | The copyright for this article belongs to Authors. |
| Keywords: | complementary DNA; glyceraldehyde 3 phosphate dehydrogenase; hur antibody; immunoglobulin G; monoclonal antibody; paraspeckle component 1; recombinant paraspeckle component 1 protein; recombinant protein; ribonuclease inhibitor; ribosomal protein s5; ribosome protein; RNA binding protein; unclassified drug; virus RNA; protein binding; ribosomal protein S5; ribosome protein; RNA binding protein; virus RNA, 5' untranslated region; antiviral activity; Article; binding site; cellular distribution; chemiluminescence immunoassay; confocal microscopy; consensus development; controlled study; cross linking; crosslinking immunoprecipitation; densitometry; gene expression; gene silencing; genetic transcription; genetic transfection; hepatitis C; Hepatitis C virus; Huh-7.5 cell line; human; human cell; image analysis; immunofluorescence microscopy; internal ribosome entry site; isolation and purification; nonhuman; paraspeckle; plasmid; polyacrylamide gel electrophoresis; polysome; protein binding; protein expression; protein purification; radiolabeling; real time polymerase chain reaction; real time reverse transcription polymerase chain reaction; RNA immunoprecipitation; RNA isolation; RNA sequencing; RNA translation; translation termination; virus infection; virus replication; Western blotting; genetics; Hepacivirus; hepatitis C; host pathogen interaction; metabolism; physiology; protein synthesis; virology; virus replication, Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Internal Ribosome Entry Sites; Protein Binding; Protein Biosynthesis; Ribosomal Proteins; RNA, Viral; RNA-Binding Proteins; Virus Replication |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 07 Aug 2024 06:09 |
| Last Modified: | 07 Aug 2024 06:09 |
| URI: | http://eprints.iisc.ac.in/id/eprint/85253 |
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