December 1st, 2024
Recent Publications Harnessing the Power of Translatomics
Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.
In this week’s Sunday papers, Chi et al. revealed the significant regulatory roles of PCBP1-AS1 protein in host-pathogen interactions, which could be the potential target for antiviral strategies aimed at disrupting the influenza virus life cycle. Lin et al. showed Lnc557, a lncRNA, regulated host cellular processes to facilitate BmNPV viral infections. Li et al. identified that VP3 protein of Senecavirus A enhanced viral translation and modulated host protein localization for immune evasion.
A small protein encoded by PCBP1-AS1 is identified as a key regulator of influenza virus replication via enhancing autophagy
PLoS Pathogens, 2024
Chi, X., Huang, G., Wang, L., Zhang, X., Liu, J., Yin, Z., Guo, G., Chen, Y., Wang, S. and Chen, J.L.
Influenza A virus (IAV) is highlighted as a significant pathogen responsible for seasonal flu outbreaks and pandemics. The study focused on understanding the molecular mechanisms that facilitate IAV replication within host cells.
PCBP1-AS1 is a long non-coding RNA (lncRNA), which was thought to be non-protein-coding. In this study, the authors discovered that PCBP1-AS1 encoded a functional small protein, namely PCBP1-AS1 encoded small protein (PESP) that is critical for influenza virus replications. PESP plays a pivotal role in enhancing autophagy to accelerate cellular degradation.
The ribosome profiling data in the study unveiled that the long non-coding RNA PCBP1-AS1 harboured an actively translated open reading frame (ORF) that encodes a small protein. This analysis challenged the traditional view of PCBP1-AS1 as a non-coding RNA. Ribosome footprints precisely mapped to this ORF, confirming active translation and suggesting its significance in cellular and viral processes.
The authors identified the PCBP1-AS1 protein as a novel regulator of autophagy and a potential target for antiviral strategies aimed at disrupting the influenza virus life cycle. This highlights small proteins as pivotal players in host-pathogen interactions.
Lnc557 promotes Bombyx mori nucleopolyhedrovirus replication by interacting with BmELAVL1 to enhance its stability and expression
Pesticide Biochemistry and Physiology, 2024
Lin, S., Shen, Z.Y., Wang, M.D., Zhou, X.M., Xu, T., Jiao, X.H., Wang, L.L., Guo, X.J. and Wu, P.
The study uncovered a critical role of the long non-coding RNA (lncRNA) Lnc557 in promoting Bombyx mori nucleopolyhedrovirus (BmNPV) replication. Researchers found that Lnc557 binds to BmELAVL1, an RNA-binding protein in the host silkworm, stabilizing it and increasing its expression. Elevated levels of BmELAVL1 enhance the replication efficiency of BmNPV.
Ribosome profiling was used to distinguish coding from non-coding RNAs and in elucidating the functional roles of lncRNAs. The analysis revealed that Lnc557 did not encode a protein to regulate BmNPV. Unlike coding RNAs with active ribosome occupancy, Lnc557 showed minimal ribosome association, confirming its non-coding nature.
Functional analyses demonstrated that silencing Lnc557 significantly reduced viral replication, while its overexpression promoted it. This study also underscored the broader significance of lncRNAs in pathogen-host dynamics, offering insights into their potential roles in other viral systems. These findings pave the way for innovative biotechnological interventions to protect the silkworm industry and manage lncRNA-mediated infections.
VP3 protein of Senecavirus A promotes viral IRES-driven translation and attenuates innate immunity by specifically relocalizing hnRNPA2B1
Journal of Virology, 2024
Li, L., Li, X., Zhong, H., Li, M., Wan, B., He, W., Zhang, Y., Du, Y., Chen, D., Zhang, W. and Ji, P.
Senecavirus A (SVA) is a virus that affects livestock and has been associated with vesicular disease. VP3 protein of SVA was identified to promote viral replication and immune evasion. VP3 enhanced viral translation by specifically promoting internal ribosome entry site (IRES)-driven translation, which is a mechanism that allows the virus to efficiently use the host cell’s translation machinery for its own protein synthesis. The polysome profiling data showed that in the presence of VP3, the viral mRNA was more efficiently associated with polysomes, indicating an increase in active translation.
The viral proteins achieved the suppression of host’s immune response by relocalizing the host RNA-binding protein hnRNPA2B1, which is involved in immune regulation. By sequestering hnRNPA2B1 away from its immune-related functions, VP3 weakens the host’s antiviral defences.
These findings highlight the dual role of VP3 in enhancing viral translation and subverting host immunity, providing new insights into the molecular mechanisms of SVA pathogenesis and potential avenues for antiviral interventions targeting VP3 and its interactions with host proteins.