Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines

Round 1

Reviewer 1 Report

Polyamines are vital for eukaryotic cell proliferation. The most important cellular function of polyamines in cell growth is their role in facilitating translation globally as well as promoting translation of specific genes, polyamine modulons. Polyamines and its biosynthetic enzymes are under circadian rhythm control. The authors examined the effects of polyamine depletion by DFMO on the expression of the eight circadian clock genes at the transcriptional and translational levels. They found that the transcription of RORa is downregulated in polyamine depleted in NIN3T3 ells. Most importantly, they report that the two genes, BML1 and REV-ERBa genes are regulated by polyamines at the level of translation and that polyamines enhance translation of these genes by a ribosome shunt mechanism, thereby adding two more genes to the list of eukaryotic polyamine modulons. The work was carefully designed and executed and the data provides solid support for their conclusion. This is an interesting study acceptable for publication in the International Journal of Molecular Sciences.

Reviewer 2 Report

The overall goal of this study was to determine the role of polyamines in circadian clock.  The authors showed that in NIH3T3 cells the depletion of polyamines lengthened the circadian period of clock genes.  Moreover, they show that Bmal1 and Rev-erb α were part of a polyamine modulon.

The authors conducted a thorough investigation.  The conclusions were supported by the data and the experimental design was appropriate for the question asked.

This is an impressive body of work and gives yet another example of the importance of the polyamines.