Adachi Yuka, Umeda Mana, Kawazoe Asako, Sato Tetsuya, Ohkawa Yasuyuki, Kitajima Sakihito, Izawa Shingo, Sagami Ikuko, Taketani Shigeru
Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585, Japan.
Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
Arch Biochem Biophys. 2017 Oct 1;631:19-29. doi: 10.1016/j.abb.2017.08.006. Epub 2017 Aug 9.
Heme plays a role in the regulation of the expression of genes related to circadian rhythms and heme metabolism. In order to identify new heme-regulated proteins, an RNA sequence analysis using mouse NIH3T3 cells treated without or with 5-aminolevulinic acid (ALA) was performed. Among the changes observed in the levels of various mRNAs including heme oxygenase-1 (HO-1) and ALA synthase-1 (ALAS1), a mouse homologue of the plant circadian-regulating protein SRR1, SRR1 domain containing (SRRD) was induced by the ALA treatment. The expression of SRRD was dependent on heme biosynthesis, and increased the production of heme. SRRD was expressed under circadian rhythms, and influenced the expression of clock genes including PER2, BMAL1, and CLOCK. The knockout of SRRD arrested the growth of cells, indicating that SRRD plays roles in heme-regulated circadian rhythms and cell proliferation.
血红素在昼夜节律和血红素代谢相关基因的表达调控中发挥作用。为了鉴定新的血红素调节蛋白，对未处理或用5-氨基乙酰丙酸（ALA）处理的小鼠NIH3T3细胞进行了RNA序列分析。在包括血红素加氧酶-1（HO-1）和ALA合酶-1（ALAS1）在内的各种mRNA水平观察到的变化中，植物昼夜节律调节蛋白SRR1的小鼠同源物、含SRR1结构域（SRRD）受ALA处理诱导。SRRD的表达依赖于血红素生物合成，并增加了血红素的产生。SRRD在昼夜节律下表达，并影响包括PER2、BMAL1和CLOCK在内的时钟基因的表达。SRRD基因敲除使细胞生长停滞，表明SRRD在血红素调节的昼夜节律和细胞增殖中发挥作用。
