Biology subjects

Sohier, T. J.

Publications and source records attributed to Sohier, T. J..

3 recordsLinked to original sources

bioRxiv2026

Viral Infections Drive Functional Remodeling of Ribosome-Associated Proteins

Viruses hijack host ribosomes to synthesize their proteins and have evolved various strategies to manipulate translation, including the association of numerous non-ribosomal proteins, known as ribosome-associated proteins (RAPs), with the core ribosome. However, current methods of capturing RAPs that associate transiently and/or in small amounts with ribosomes are suboptimal. To address this issue, we developed an enhanced ribosome affinity purification (eRAP) method that enables the capture of over 500 previously unreported RAPs. Using eRAP, we investigated whether the composition of ribosomes changes during infection by two very different viruses: herpes simplex virus 1 (HSV-1) and Sindbis virus (SINV). Our results revealed that viral infection does not substantially alter the composition of core ribosomes but does drive extensive remodeling of RAPs in a virus-specific manner. Functional analyses with SINV showed that several of these RAPs are critical for viral propagation. Additionally, we discovered that the RAP ASCC3 plays a novel role in promoting the expression of secretory proteins, including viral glycoproteins. This occurs independently of ASCC3s canonical function of rescuing ribosome collisions. Together, our findings establish the ribosome as a dynamic regulatory hub that undergoes remodeling to achieve virus-specific translational output, highlighting the functional significance of ribosomal heterogeneity.

molecular biology↗

bioRxiv2022

Extensive uORF translation from HIV-1 transcripts conditions DDX3 dependency for expression of main ORFs and elicits specific T cell immune responses in infected individuals

Human immunodeficiency virus type-1 (HIV-1) is a complex retrovirus which relies on alternative splicing, translational and post-translational mechanisms to produce more than 15 functional proteins from its single [~]10kb transcriptional unit. Here, we have applied ribosome profiling and nascent protein labeling at different time points during infection of CD4+ T lymphocytes to characterize the translational landscape of cellular and viral transcripts during the course of infection. Our results indicate a strong impact of viral infection on host cellular transcript levels but a modest impact on global translation rates. Analysis of ribosome profiling reads from viral transcripts reveals extensive and productive non-AUG translation of small peptides from multiple upstream open reading-frames (uORFs) located in the 5 long terminal repeat. Remarkably, these uORFs derived peptides elicit specific T cell responses in HIV-infected individuals. uORFs are conserved among other retroviruses and, together with the TAR sequence, condition the dependency on DDX3 for efficient translation of the main viral open-reading frames.

microbiology↗

bioRxiv2018

Understanding RNP remodelling uncovers RBPs functionally required for viral replication

The compendium of RNA-binding proteins (RBPome) has been greatly expanded by the development of RNA-interactome capture (RNA-IC). However, it remains unknown how responsive is the RBPome and whether these responses are biologically relevant. To answer these questions, we created comparative RNA-IC to analyse cells challenged with an RNA virus, called sindbis (SINV). Strikingly, the virus altered the activity of 245 RBPs, many of which were newly discovered by RNA-IC. Mechanistically, alterations in RNA binding upon SINV infection are caused by changes in the subcellular localisation of RBPs and RNA availability. Moreover, RBPome responses are crucial, as perturbation of dynamic RBPs modulates the capacity of the virus to infect the cell. For example, ablation of XRN1 causes cells to be refractory to infection, while GEMIN5 moonlights as a novel antiviral factor. Therefore, RBPome remodelling provides a mechanism by which cells can extensively rewire gene expression in response to physiological cues.\n\nHIGHLIGHTSO_LIA quarter of the RBPome remodels upon SINV infection.\nC_LIO_LIThe remodelling is caused by changes in protein localisation and RNA availability.\nC_LIO_LIRewiring of the RBPome is crucial for viral infection efficacy.\nC_LIO_LIWe discover RBPs with previously unknown anti- or pro-viral activity.\nC_LI

molecular biology↗