Pseudogenes, a sub-class of long non-coding RNA (lncRNA) that developed from the genome's 20,000 protein-coding genes but lost the ability to produce proteins, have long been considered nothing more than genomic "junk". Yet the retention of these 20,000 mysterious remnants during evolution has suggested that they may in fact possess biological functions and contribute to the development of disease.
The Cancer Research Institute at Beth Israel Deaconess Medical Center (BIDMC) researchers have provided some of the first evidence that one of these non-coding "evolutionary relics" actually has a role in causing cancer. The scientists report that independent of any other mutations, abnormal amounts of the BRAF pseudogene led to the development of an aggressive lymphoma-like disease in a mouse model, a discovery that suggests that pseudogenes may play a primary role in a variety of diseases.
Importantly, the new discovery also suggests that with the addition of this vast "dark matter" the functional genome could be tremendously larger than previously thought - triple or quadruple its current known size.
Senior author Pier Paolo Pandolfi explained that their mouse model of the BRAF pseudogene developed cancer as rapidly and aggressively as it would if you were to express the protein-coding BRAF oncogene, adding that it's remarkable that this very aggressive phenotype, resembling human diffuse large B-cell lymphoma, was driven by a piece of so-called 'junk RNA.'
Pandolfi added that as attention turns to precision medicine and the tremendous promise of targeted cancer therapies, all of this vast non-coding material needs to be taken into account. In the past, they have found non-coding RNA to be overexpressed, or misexpressed, but because no one knew what to do with this information it was swept under the carpet. Now they can see that it plays a vital role.
Pandolfi noted that they have to study this material, they have to sequence it and they have to take advantage of the tremendous opportunity that it offers for cancer therapy.