Fruit flies and plants have independently come up with similar ways to mark time, a new study suggests.
Both modify the products of certain genes based on daily rhythms set by the organisms’ circadian clocks, the study shows. The finding, published online October 20 in Nature, may help scientists better understand how plants and animals respond to light-dark cycles.
Most research on circadian clocks has focused on the process by which the biological timekeepers turn genes on and off. But the new study shows that the clocks also govern how molecules of RNA that are transcribed from a gene are spliced together for translation into the gene’s protein product.
“This paper certainly adds a very novel twist,” says Yi Liu, a biologist at the University of Texas Southwestern Medical Center at Dallas who was not involved in the study.
Marcelo Yanovsky, a plant physiologist and geneticist at the IFEVA Institute of Agronomy and the Fundación Instituto Leloir in Buenos Aires, Argentina, and his colleagues searched for genes in the plant Arabidopsis thaliana that cause it to raise its leaves to the light during the day and let them droop back down in the dark. The researchers found a form of the plant that moved its leaves out of sync with the usual 24-hour rhythm, in a 30-hour cycle, and traced the source of the longer cycle to a mutation in the gene PRMT5.
PRMT5 makes an enzyme that adds methyl groups to histone proteins — proteins that form spools on which DNA is wound to fit inside cells. The addition of the chemical tag causes DNA to pack more tightly and shuts down gene activity. The team found that the enzyme also adds methyl groups to proteins involved in cutting and pasting RNA molecules that will later be made into proteins.
The cut-and-paste process is known as alternative splicing, and it allows cells to create different versions of proteins much the way that film editors can splice scenes together to produce movies with alternative endings. By adding methyl groups to proteins involved in selecting where to cut the RNA molecule, the interaction with some weak cutting sites is strengthened, the researchers discovered. It is unclear how adding the chemical tags beefs up the interaction between the proteins and RNA.
Yanovsky’s team found that the circadian clock governs the activity of PRMT5 in Arabidopsis plants, and that PRMT5, in turn, controls the pace at which the clock ticks by regulating splicing of an important clock component. The discovery is the first indication that RNA splicing follows a daily rhythm.
Circadian clocks in plants and animals work similarly, though the gears that drive them are different as the works in a cuckoo clock and a pocket watch. But animals do have a gene called DART5 that is equivalent to PRMT5.
In order to find out if RNA splicing in animals also punches the clock, Yanovsky and his colleagues tested fruit flies in which DART5 was mutated and found that the flies move around at different times of day than normal. In flies, the circadian clock doesn’t control production of the enzyme, but the enzyme does help time the splicing of clock components and other protein-producing RNAs.
The fact that two clocks with different gears use the same enzyme to control alternative splicing “raises some interesting evolutionary questions,” says Stacey Harmer, a plant biologist at the University of California, Davis.
Yanovsky and his colleagues suggest that because PRMT5 plays similar, but not identical, roles in daily rhythms in Arabidopsis and fruit flies, the time-keeping mechanism probably evolved separately in plants and animals. That explanation is the most likely, Harmer says, but “there’s that tantalizing possibility that there might be something else going on.”
One idea is that the mechanism is a remnant of an ancient chemical clock that operated in a common ancestor of plants and animals, but evidence in support of that hypothesis is lacking in this case, she says.
