A splice variant of human Bmal1 acts as a negative regulator of the molecular circadian clock

Circadian rhythms: Alternative forms of clock protein have opposing effects An alternative form of a key ‘clock’ protein involved in the maintenance of daily cellular rhythms serves as a negative regulator of the cell’s 24-hour cycle. A team led by Ilmin Kwon from Sungkyunkwan University School of Medicine, Suwon, and Kyungjin Kim from Daegu Gyeongbuk Institute of Science and Technology, both in South Korea, detailed the function of BMAL1a, a lesser-studied variant of the clock protein BMAL1b, in human cells. Whereas BMAL1b enters the nucleus, where it works in concert with another protein called CLOCK to control circadian dynamics, BMAL1a stays in the cytoplasm, where it binds BMAL1b and CLOCK, interfering with their function. Genetically inhibiting BMAL1a helped restore normal rhythmic cycles. Drugs targeting BMAL1a may thus aid in sleep disorders and other circadian-linked health problems.