Jungmin Lee

Rho-dependent Termination of ssrS (6S RNA) Transcription in Escherichia coli IMPLICATION FOR 3′ PROCESSING OF 6S RNA AND EXPRESSION OF DOWNSTREAM ygfA (PUTATIVE 5-FORMYL-TETRAHYDROFOLATE CYCLO-LIGASE)

It is well known that 6S RNA, a global regulatory noncoding RNA that modulates gene expression in response to the cellular stresses in Escherichia coli, is generated by processing from primary ssrS (6S RNA) transcripts derived from two different promoters. The 5′ processing of 6S RNA from primary transcripts has been well studied; however, it remains unclear how the 3′-end of this RNA is generated although previous studies have suggested that exoribonucleolytic trimming is necessary for 3′ processing. Here, we describe several Rho-dependent termination sites located ∼90 bases downstream of the mature 3′-end of 6S RNA. Our data suggest that the 3′-end of 6S RNA is generated via exoribonucleolytic trimming, rather than endoribonucleolytic cleavage, following the transcription termination events. The termination sites identified in this study are within the open reading frame of the downstream ygfA (putative 5-formyl-tetrahydrofolate cyclo-ligase) gene, a part of the highly conserved bacterial operon ssrS-ygfA, which is up-regulated during the biofilm formation. Our findings reveal that ygfA expression, which also aids the formation of multidrug-tolerant persister cells, could be regulated by Rho-dependent termination activity in the cell.

Antioxidant and mitochondrial protective effects of oxidized metabolites of oltipraz

Importance of the field: Comprehensive studies indicate that oltipraz exerts cancer chemopreventive effects. Oltipraz has other therapeutic potentials, which include anti-fibrotic effect, inhibition of insulin resistance, mitochondrial protection and cytoprotective effect against oxidative stress. Although antioxidant mechanisms may account for its cancer chemopreventive effect, details on the molecular mechanism still remain to be clarified. Areas covered in this review: Two major metabolic pathways of oltipraz include oxidative desulfuration of the thione to yield 4-methyl-5-(pyrazin-2-yl)-3H-1,2-dithiol-3-one and molecular rearrangement to 7-methyl-6,8-bis(methylthio)H-pyrrolo[1,2-a]pyrazine. In addition to the diverse pharmacological effects of oltipraz, the oxidized metabolites may have distinct biological effects on cell survival. The AMP-activated protein kinase pathway has been recognized as a key cascade for mitochondrial protection and cell survival events, which can be activated by the oxidized metabolites of oltipraz. What the reader will gain: In this review, the metabolic activation of oltipraz and the role of the cell signaling pathways in regulating the expression of Phase II genes and antioxidant activity are discussed with particular reference to their effects on mitochondrial protection and cell survival. Take home message: In terms of therapeutic potential, the findings reviewed here demonstrate a therapeutic potential for oxidized metabolite of oltipraz and offer comparison of antioxidant capacity between metabolites and parent compound.