Protein breakthrough sheds new light on kidney disease, cancer, mental retardation
McGill researchers discover how Bicaudal-C protein controls RNA synthesis of other proteins
McGill University researchers have uncovered the long sought-after mechanism that controls the synthesis of a specific protein in fruit flies, a breakthrough with important implications for the understanding of polycystic kidney disease, cancer and mental retardation in humans, according to a study published in the November issue of the journal Developmental Cell.
The study was led by Dr. Paul Lasko, Chair of McGill's Department of Biology, with colleagues from McGill and France's Centre national de la recherche scientifique (CNRS). It was funded by the National Cancer Institute of Canada (NCIC).
Their research focused on the Bicaudal-C protein found in Drosophila, a genus of fruit fly, and how it controls the process by which ribonucleic acid (RNA) synthesizes other proteins. Bicaudal-C is one of the estimated 77 per cent of genes implicated in human disease that have obvious counterparts in fruit flies. Dr. Lasko and his colleagues discovered that Bicaudal-C controls how much protein the RNA molecule can synthesize by controlling the length of the RNA molecule's poly(A) tail – a chain of adenine nucleotides at the end of the molecule. It does this by recruiting an enzyme called CCR4 deadenylase, which chews off segments of the poly(A) tail.
In fruit flies, Bicaudal-C plays an important role in the development of embryos. "When there isn't enough Bic-C produced in the mother, then the embryos have patterning defects," said Dr. Lasko. Insufficient Bicaudal-C in the mother produced embryo flies with two posteriors and no anterior. Too much, or "overexpressed," Bicaudal-C produced embryos with a posterior and no anterior at all.
This is of great interest to researchers, Dr. Lasko explained, because the counterpart protein in humans plays a role not in the development of embryos, but in the onset of a wide variety of disorders and diseases, particularly polycystic kidney disease. To date, said Dr. Lasko, there have been no studies of the human counterpart of the Bicaudal-C protein.
"We hope our study will guide people working on the human counterpart gene to look for the same type of function, to find RNAs that are specific to kidney development. This protein is also related quite closely to the protein which leads to Fragile-X Syndrome, the most common mental retardation syndrome," he continued. "And our research has been funded by the National Cancer Institute of Canada because of the relationship between this gene and other RNA binding proteins that have been implicated in cancer."