🧬 Scientists Just Found a Hidden Layer of the Mammalian Genome

Our genes may be considerably more combinatorial than we realized.

Researchers have discovered that mammalian cells can take pieces of RNA copied from completely different genes — sometimes located on different chromosomes — and splice them together into a single messenger RNA. That hybrid RNA can then be used to manufacture a new protein containing parts encoded by both genes.

Using direct RNA sequencing, the team detected more than 30,000 candidate chimeric RNAs in mouse immune cells and more than 900 in human macrophages. Crucially, they then showed that at least one of these strange hybrids is not biological noise.

In mice, an inflammatory response causes two genes called Gsdmd and Tmem106a to combine into a chimeric RNA. Its resulting hybrid protein helps accelerate pyroptosis — the dramatic process in which infected immune cells rupture and release inflammatory signals. When researchers specifically blocked the hybrid protein, the mice became worse at controlling Salmonella infection. But they were also dramatically more resistant to lethal inflammation in a sepsis model.

Even stranger, inflammation appears to physically reorganize the genome: normally distant chromosome regions move closer together inside the nucleus, helping their RNA transcripts combine.

There is a major caveat. The detailed functional experiments were performed in mice. Similar chimeric RNAs exist in human immune cells, but scientists have not yet established what most of them do. The researchers themselves say it could take years to map their biological importance.

Still, if the phenomenon is widespread, our current catalogue of proteins may be missing an entire class of molecules hiding in combinations of genes we already thought we understood.

We finished sequencing the human genome more than two decades ago.

Apparently, reading the instruction manual was another problem entirely.

#Genetics #Biology #RNA #Genome #Immunology #Biotechnology #Science

https://www.nature.com/articles/s41586-026-10982-x