Methods and apparatuses are disclosed for handling uplink transmission in a wireless communication system. In one method, a user equipment (UE) connects to at least two base stations including a first base station controlling a first serving cell and a second base station controlling a second serving cell. The method further includes the UE receiving a downlink signaling in the second serving cell. The method also includes the UE transmitting a reference signal in the first serving cell in response to the reception of the downlink signaling.