In findings with major implications for the genetics of cancer and human health, researchers at Beth Israel Deaconess Medical Center (BIDMC) and two other science teams in New York City and Rome have uncovered evidence of powerful new genetic networks and showed how they may work to drive cancer and normal development.
Four papers published online in the almanac Cell describe aspects of what may be a fundamentally new dimension of genetic occupation that involves a vast posse of RNA molecules interacting and manipulating the molecular endgame behind the scenes.
Each report used a different approach, strengthening the basic discovery of the new RNA network. In the half-century old inside dogma of molecular biology, DNA issues its genetic blueprint to messenger RNA, which relays the orders to the protein-making machinery of the room.
The new studies suggest a significant new role for RNA on top of its traditional middle-management job: The RNA of one gene can curb and be controlled by dozens or hundreds of RNAs of other genes. In the envelope of a major tumor suppressor gene, PTEN, a shift in the associated RNA network appears to be as malevolent as a modifying in the gene itself in human prostate and colon cancer cells, in glioblastoma cells, and in a mouse subject of melanoma, according to three of the papers.
The findings may distend the framework for investigating how tumors form and progress, who is at risk for cancer, and how to rouse and disable the essential misbehaving molecules that drive the wart and spread of cancer.
"For instance, we now know that the PTEN tumor suppressor gene is talking to a cyclopean unrecognized RNA network," said Pier Paolo Pandolfi MD PhD, gaffer of the Cancer Genetics Program at BIDMC and George C. Reisman Professor of Remedy at Harvard Medical School, and the senior author of two of the papers. "The RNAs talk including a new language. If this language is broken and the RNA network is perturbed, PTEN goes down, and this has penetrating consequences. But it's incredibly exciting for therapeutic possibilities. You may be able to rewire the crosstalk between the RNAs for cancer arrest and therapy."
Scientists typically use genetic studies to search how changes in the DNA code influence the action of the proteins. Targeted therapies enjoy arisen from efforts to counteract the effect of problematic proteins, yet most of the genetic determinants of cancer residue a vexing puzzle. The newly discovered RNA network could explain much of the transitory genetic variation underlying cancer and other diseases, say authors of the papers.
The new RNA regulatory network also appears to go into the massive non-protein-coding region of the human genome and plays an substantial role in normal muscle development, suggests another related MS in Cell. Because humans share so many protein-coding genes with other organisms, including worms and yeast, this chiefly portion that is transcribed into non-coding RNA makes the human genome idiosyncratic. Much of the function of that non-coding RNA has been a mystery.
