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DIS3 ribonuclease prevents the cytoplasmic accumulation of lncRNAs carrying non-canonical ORFs, which represent a source of cancer immunopeptides.


Foretek D. et al.

Around 12% of multiple myeloma (MM) cases harbour mutations in DIS3, which encodes an RNA decay enzyme that controls the turnover of some long noncoding RNAs (lncRNAs). Although lncRNAs, by definition, do not encode proteins, some can be a source of (poly)peptides with biological importance, such as antigens. The extent and activities of these “coding” lncRNAs in MM are largely unknown. Here, we showed that DIS3 depletion results in the accumulation in the cytoplasm of 5162 DIS3-sensitive transcripts (DISTs) previously described as nuclear-localised. Around 14,5% of DISTs contain open reading frames (ORFs) and are bound by ribosomes, suggesting a possibility of translation. Transcriptomic analyses identified a subgroup of overexpressed and potentially translated DISTs in MM. Immunopeptidomic experiments revealed association of some DISTs’ derived peptides with major histocompatibility complex class I. Low expression of these transcripts in healthy tissues highlights DIST-ORFs as an unexplored source of potential tumour-specific antigens.

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D-Plex small RNA-seq

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Published
June, 2023

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  • Small RNA library preparation with UMI for Illumina
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