Gaul's new research shows that it is microRNAs that stand between a cell's survival and its death at the hands of Hid, Grim and Reaper. The microRNAs bind to the messenger RNA of the death genes and prevent their proteins from being made. But when the microRNAs are blocked, Hid, Grim and Reaper proteins are produced, causing massive cell death and killing the fly embryo.
The microRNAs that block cell death all belong to the largest microRNA family in the fruit fly. The family is made up of 13 members, which are identical in sequence at one end but different at the other. There has been some debate on whether differences at this end are important, but Gaul's research now shows that they are central for helping the microRNAs find the right targets.
"Our findings show that while similar defects are seen when the different family members are blocked, they are not identical," Gaul says. "And we find that different family members interact differently with the three death genes."
Deciding between life and death is only one of many split-second decisions that a cell may have to make. By regulating which messenger RNAs are used to make protein, microRNAs can help cells react to an event without the nucleus being involved. For example, the ending of a nerve cell can be very far away from its nucleus. Localizing and regulating messenger RNAs at the nerve endings enables the nerves to react very fast to an incoming signal, instead of every signal being transmitted to the nucleus and back.
Gaul's lab has many more interesting microRNAs to examine, a number of which are conserved between flies and humans. The next experiments will look to further match up different microRNAs with their targets. But Gaul is also very interested in how microRNAs themselves are regulated.