Deciphering a Serum Peptide Activity Associated with Biologic Clock

Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria. The periodic rhythm is roughly 24-hour cycle in biochemical, physiological, or behavioral processes in organisms. Although circadian rhythms are endogenously-driven, an organism’s circadian clock is adjusted to the environmental stimuli and must maintain the periodicity of biologic rhythm despite the changing kinetics in cellular activities. Some cellular proteins are believed to be associated with circadian rhythms. In this study, deficiency of a serum protein in human subjects was detected in individuals diagnosed with sleep disorders. N-terminal sequence analysis of the short peptide with BLAST sequence alignment software on NCBI indicated that it might be related to the protein named Hlark (human lark protein). Lark is required for embryonic development, and is, in fact, RBM4, a splicing regulator. RBM4 is crucial for targeting to speckles. This finding is consistent with the potential existence of a novel sub-nuclear targeting pathway. RBM4 and Lark is probably the same protein and are localized in speckles and nucleoli, but can redistribute to peri-nucleolar clusters, consistent with a novel sub-nuclear pathway.