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Viktor Yurevych

Viktor Yurevych

PhD student

Analysis of tumor translatomes & novel microproteins in pediatric malignancies

Phone 31 (0) 88 97 25186

Apart from mRNAs, mammalian genomes contain multiple classes of RNA transcripts that undergo polyadenylation, capping and splicing, but may not code for protein. Long non-coding RNAs (lncRNAs) are one class of these transcripts. By definition, non-coding RNAs would not encode proteins, as is normally assumed during gene annotation.

However, evidence from ribosome profiling experiments indicates that a significant proportion of lncRNAs generate microprotein products less than 100 aminoacids in length. Owing to their relatively recent discovery, only a tiny fraction of human microproteins have been investigated for their functions in development and disease. As some lncRNAs have been implicated in cancer, including pediatric malignancies, whether the RNA or the microprotein is responsible for the cancer-related functionality remains an open question.

We plan to catalog and characterize novel microproteins across multiple pediatric cancer types through application of ribosome profiling (or Ribo-seq), mass spectrometry, transcriptomic and interactome analyses. In combination with targeted knock-in/out and knockdown assays we plan to identify the precise functions of the detected microproteins within our target systems.

Another potential application of microproteins is their use as novel epitopes for highly tumor-specific immunotherapy due to the specificity of lncRNA expression in tumors as well as generation of aberrant translation products over the course of treatment. We plan to generate personalized, patient-specific neoantigen databases for precise targeting using immunotherapeutics.