The novel heme-dependent inducible protein, SRRD regulates heme biosynthesis and circadian rhythms

Arch Biochem Biophys. 2017 Oct 1;631:19-29. doi: 10.1016/ 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.

Keywords: ALA; Circadian rhythms; Heme biosynthesis; Knockout; PER2; SRRD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / pharmacology
  • Animals
  • CLOCK Proteins / genetics
  • Cell Proliferation
  • Circadian Rhythm Signaling Peptides and Proteins / genetics*
  • Circadian Rhythm Signaling Peptides and Proteins / metabolism
  • Circadian Rhythm*
  • Gene Expression Regulation / drug effects
  • Gene Knockout Techniques
  • Heme / metabolism*
  • Mice
  • NIH 3T3 Cells
  • RNA, Messenger / genetics


  • Circadian Rhythm Signaling Peptides and Proteins
  • RNA, Messenger
  • Srrd protein, mouse
  • Heme
  • Aminolevulinic Acid
  • CLOCK Proteins
  • Clock protein, mouse