Researchers at Harvard Medical School say they have uncovered an entirely new gene regulation system in mammals, one that allows instructions from different genes, including genes on different chromosomes, to combine and produce previously unknown functional proteins. The findings, published on Sept. 2 in Nature, suggest that the mammalian genome may be far more biologically complex than scientists had understood.
A new layer of biology emerges
The team reported that the phenomenon centers on chimeric mRNAs, formed when segments from separate genes are joined together. Using direct RNA sequencing, the researchers compiled a list of more than 30,000 chimeric mRNAs observed at least once in mammalian cells and profiled nearly 400 that were regulated by inflammatory signals, including chimeric mRNAs conserved in both human and mouse immune cells.
The study indicates that healthy chromosomes can loop together during an immune response, bringing normally distant genes into proximity and allowing the production of hybrid proteins. According to the researchers, this may represent a previously overlooked aspect of mammalian biology with implications for disease research and drug discovery. Source
Testing whether the proteins are functional
To determine whether these chimeric RNAs do more than simply exist, the researchers examined one example in mice involving the genes encoding GSDMD and TMEM106A. They confirmed that the resulting chimeric protein, GSDMD-TMEM106A, occurred naturally in mice and was produced as part of the immune response in cells from two different strains of lab mice as well as a wild-derived strain.
The team also developed a genetic tool designed to stop production of the chimeric protein without affecting the standard GSDMD and TMEM106A proteins. That approach helped establish that the hybrid molecule is not just a sequencing artifact, but a biologically relevant product in mammals.
Potential implications for disease and treatment
Researchers said the discovery could open new directions for understanding poorly explained disease processes and identifying novel drug targets. They emphasized that they do not yet know how widespread the phenomenon is, but the evidence already points to a much broader range of molecules and proteins that cells may be capable of making.
While the work is still at an early stage, the study adds a new dimension to genetic research and could reshape how scientists think about protein diversity in human health and disease. Source
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