Research Paper Volume 5, Issue 10 pp 741—758

TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants


Figure 6. TAF-4 and HIF-1 are Required for clk-1(qm30) Life Extension.

(a) Survival curves for clk-1(qm30); Pgst-4::GFP transgenic worms cultured on RNAi targeting each of seven transcription factors required for isp-1(qm150) life extension. For this panel, as well (b) and (c), a summary of lifespan data and significance testing is provided in Supplementary File 3 and Table II. (b) In the absence of the Pgst-4::GFP reporter, clk-1(qm30) remains surprisingly recalcitrant to any life-shortening effect of the seven RNAi clones. Only taf-4 and hif-1 RNAi significantly shorten lifespan. (c) Survival analysis of clk-1(qm30), clk-1(e2519) and N2 wild-type animals cultured on standard NGM/OP50 plates. Mean lifespan of each strain is 29.5, 21.3, 18.8 days, respectively. Both qm30 and e2519 are significantly longer-lived than N2 (p=0.049 and 1.3E-09, respectively. (N=60 worms/trace, for all panels). (D) Model depicting role of TAF-4 in Mit mutant life extension. TAF-4 is a component of the general transcription machinery leading to recruitment of RNA Pol II to basal promoters. CREB contains binding sites for TAF-4, CRTC-1 and CBP. AMPK activation inhibits the interaction of CBP and CRTC-1 with CREB. Loss of TAF-4 blocks Mit mutant life extension, so too does removal of AMPK.