RNA and proteins have long been known to interact, but classic molecular biology pretty much had proteins down as something that modified RNA function. Not so for BMOR, a long nonCoding RNA (1,247 nucleotides) expressed in breast cancer cells metastatic to the brain. BMOR binds to IRF3 (Interferon Regulatory factor 3) inhibiting its phosphorylation by TBK1 with subsequent movement to the nucleus where it stimulates interferon expression which then turns on hundreds of genes producing inflammation. All this is described in Proc. Natl. Acad. Sci. vol. 119 e2200230119 ’22 —
May 26, 2022
119 (22) e2200230119
Not sure if it is behind a paywall. Definitely worth a read because knocking down BMOR in breast cancer cells prevents them from spreading to the brain (probably by using BMOR to turni off the brain’s immune response to them). Even more interestingly, BMOR was found to be only substantially expressed in breast cancer metastasis to brain tissue versus breast cancer metastasis to nonbrain tissues.
Teleology as always raises its head. What in the world is the normal function of BMOR? It can’t be what it is doing in the animal model described here. Why would a cell make something to help it kill the organism containing it?
Then of course, as is typical of all interesting research, larger questions are raised. Are there other RNAs whose function is to modify protein function? Remember that 75% of the genome is transcribed into RNA. Most of this has been thought of as molecular chaff, like the turnings of a lathe. Time pick up the chaff from the factory floor and give it a look.
Chemiotics II 