Your immune system is secretly using junk DNA from ancient viruses to decide when to trigger inflammation in your body.
Human and mouse genomes are littered with the genetic remains of ancient viruses that infected our ancestors millions of years ago. These sequences were dismissed as useless debris for decades, but they are actually producing functional proteins in modern immune cells. Two of these proteins, named SYNIR and SEMR, have been caught regulating how macrophages respond to threats. These ghost viral parts act as a dial that can turn the body's inflammatory response up or down. This discovery changes our entire understanding of the immune system by showing that we are part-virus at a functional level.
Integrative Multiomics Analysis and CRISPR Screening Identify Functional Noncanonical Translation Loci in the Mouse Immune System
SSRN · 6718764
Ribosome profiling has revealed thousands of noncanonical translation events across mammalian genomes, yet functional characterization has focused predominantly on cancer cell fitness. Here, we perform a unified Ribo-seq meta-analysis across 20 mouse leukocyte datasets to define a compendium of 22,276 noncanonical coding sequences, including uORFs and ORFs on noncoding RNAs and pseudogenes, with proteogenomic validation. Two orthogonal CRISPR screens in macrophages, a fitness screen and a TLR1/T