BN seminar: Nikolina Šoštarić - Global translational analysis of human CD8+ T cells





Delft: Room A1.100 (building 58, van der Maasweg 9)


Bionanoscience (BN) seminar by dr. Nikolina Šoštarić (Sanquin Amsterdam) on "Global translational analysis of human CD8+ T cells".  The talk will start at 12:45h, and lunch is provided from 12:30h.

T cells play a central role in the human adaptive immune system by combating viruses and tumors. To effectively clear their target cells (e.g., cancer cells), T cells have to become activated, and this process requires substantial transcriptome and proteome remodelling. We and others have previously shown that mRNA expression levels in T cells are a poor proxy for the corresponding protein outputs, indicating an important role of post-transcriptional events in dictating the protein content. To decipher the changes in gene expression upon the T cell activation, we separated the cell lysates of resting and activated human CD8+ T cells into polysomal fractions (i.e., based on the number of ribosomes attached to RNA molecules) and subsequently analyzed the fractions by RNA-sequencing and MS proteomics.

Differential expression analyses showed that already upon two hours of activation, there are extensive changes in the transcriptome and the proteome. Remodelling of RNA and protein landscapes thereby occurs rapidly in T cells. To get a first glimpse at ribosomal occupancy, which is a proxy for translation, we constructed and analyzed the distribution patterns of transcripts. Overall, we observed that translation becomes more selective upon T cell activation, with only a limited group of genes shifting towards higher translation and the majority towards lower. To further pinpoint the RNA sequence features (e.g., RNA-binding protein motifs) that are linked to changes in translation, we applied classification methods from machine learning. Finally, linking the translation impact of the motifs with protein redistribution of corresponding RNA-binding proteins will allow us to learn more about post-transcriptional regulation. In conclusion, this integrated analysis will shed light on the rules that define protein expression in human CD8+ T cells.