Cyclin D1, a protein that helps push a replicating cell through the cell cycle also mediates the processing and generation of mature microRNA (miRNA), finds a new study.
The research suggests that a protein strongly implicated in human cancer also governs the non-protein-coding genome.
AdvertisementThe non-coding genome, previously referred to as junk DNA, makes up most of the human genome, and unlike the coding genome, varies greatly between species.
"In addition to its role in regulating the cell cycle, cyclin D1 induces Dicer and thereby promotes the maturation of miRNA," lead researcher Richard Pestell, M.D., Ph.D., Director of the Kimmel Cancer Center at Thomas Jefferson University and Chair of the Department of Cancer Biology, said.
Dicer is a protein that converts inactive hairpin-structured microRNA precursors into their active single stranded form.
"The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis," he said.
Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo.
In prior work, they showed that cyclin D1 regulates the non coding genome, and that the non-coding genome, in turn, regulates expression of cyclin D1.
Furthermore, the group showed that many cancer patients encode a form of cyclin D1 that evades negative feedback from the non coding genome.
These attenuating feedback loops between the non coding and coding genome may be a common theme in cancer and other biological processes.
In the current study, the group sought to investigate the mechanism by which cyclin D1 regulates the biogenesis of non coding miRNA.
Dr. Pestell and colleagues developed transgenic mice that could induce cyclin D1 expression in the breast and examined cells with cyclin D1 gene deleted.
The researchers noticed that cells lacking cyclin D1 produced less of the miRNA-processing protein, Dicer, and therefore had reduced levels of mature miRNA.
The study is published in the journal Nature Communications.