You can start this mission after finishing The Vice Assassination and going to the "L" marker on your map in the Hawick area, where you need to answer the ringing phone to begin. Lester wants you to kill a man named Isaac Penny, who is known for using the bus to get to work.
When you gain control of Franklin, grab a vehicle and head to the bus depot, where you will find a bus waiting for you. Get inside the bus and you'll need to head to each bus stop until you find your target. It isn't until the fourth stop where you find a passenger that actually talks, who is your target.
He won't get on the bus, but will steal a bike from a nearby pedestrian. Chase him down with the bus and run him over. If he isn't dead, get out and shoot him or run him over again. Once he is gone, exit the bus and get away from the scene to finish the mission.