Steroid receptor coactivator TAIMAN is a new modulator of insect circadian clock

TAIMAN (TAI), the only insect ortholog of mammalian Steroid Receptor Coactivators (SRCs), is a critical modulator of ecdysone and juvenile hormone (JH) signaling pathways, which govern insect development and reproduction. The modulatory effect is mediated by JH-dependent TAI's heterodimerization with JH receptor Methoprene-tolerant and association with the Ecdysone Receptor complex. Insect hormones regulate insect physiology and development in concert with abiotic cues, such as photo- and thermoperiod. Here we tested the effects of JH and ecdysone signaling on the circadian clock by a combination of microsurgical operations, application of hormones and hormone mimics, and gene knockdowns in the linden bug Pyrrhocoris apterus males. Silencing taiman by each of three non-overlapping double-strand RNA fragments dramatically slowed the free-running period (FRP) to 27-29 hours, contrasting to 24 hours in controls. To further corroborate TAIMAN's clock modulatory function in the insect circadian clock, we performed taiman knockdown in the cockroach Blattella germanica. Although Blattella and Pyrrhocoris lineages separated similar to 380 mya, B. germanica taiman silencing slowed the FRP by more than 2 hours, suggesting a conserved TAI clock function in (at least) some insect groups. Interestingly, the pace of the linden bug circadian clock was neither changed by blocking JH and ecdysone synthesis, by application of the hormones or their mimics nor by the knockdown of corresponding hormone receptors. Our results promote TAI as a new circadian clock modulator, a role described for the first time in insects. We speculate that TAI participation in the clock is congruent with the mammalian SRC-2 role in orchestrating metabolism and circadian rhythms, and that TAI/SRCs might be conserved components of the circadian clock in animals. Author summary Most living creatures need to synchronize their rhythmic biological functions with the 24-hour day/night cycle of Earth. Instead of pocket watches or cell phones, they use intracellular molecular clocks to anticipate the daily recurring changes. Those circadian clocks are at the genetic level remarkably conserved among mammals and insects. Here, for the first time in insects, we introduce the protein TAIMAN as a new modulator of the circadian clock. The removal of TAIMAN from the adult linden bug Pyrrhocoris apterus or the German cockroach Blattella germanica males slows the clock by 2-4 hours. Circadian clocks often adjust animals' physiology through various hormones and neuropeptides. Insect endocrinology is dominated by the steroid and steroid-like hormones, ecdysone, and juvenile hormone: and TAIMAN is closely engaged in both juvenile hormone and ecdysone receptor signaling. However, the circadian role of TAIMAN presented here modulates the clock in a hormone-independent way. Importantly, TAIMAN is related to the mammalian SRC-2 protein, which is involved in regulating circadian clock machinery in mice. Thus, the novel role we describe for TAIMAN in insects may have a counterpart in mammalian physiology.