CRISPR screens of noncanonical coding sequences and integrative multiomics uncover novel retrovirus-derived proteins

Endogenous retrovirus-derived envelope proteins are linked to functional noncanonical translation in adult mouse myeloid cells, identified via CRISPR screens in macrophages.

• Why it matters: Noncanonical translation is widespread in mammalian genomes, but its immune functions are poorly mapped beyond cancer-cell fitness assays.
• What they did: A meta-analysis of Ribo-seq from 20 mouse and 5 human leukocyte datasets defined 22,572 mouse and 18,701 human noncanonical coding sequences, then two orthogonal CRISPR screens tested viability and TLR1/TLR2-NF{kappa}B signaling in immortalized bone marrow-derived macrophages.
• The result: The screens prioritized dozens of nCDSs for follow-up and implicated retroviral envelope-derived proteins as previously unrecognized modulators of murine macrophage biology, supported by proteogenomic integration and community genome-browser resources.

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