RNase J is a conserved ribonuclease that belongs to the β-CASP family of nucleases. It possesses both endo- and exo-ribonuclease activities, which play a key role in pre-rRNA maturation and mRNA decay. Here we report high-resolution crystal structures of Deinococcus radiodurans RNase J complexed with RNA or uridine 5′-monophosphate in the presence of manganese ions. Biochemical and structural studies revealed that RNase J uses zinc ions for two-metal-ion catalysis. One residue conserved among RNase J orthologues (motif B) forms specific electrostatic interactions with the scissile phosphate of the RNA that is critical for the catalysis and product stabilization. The additional manganese ion, which is coordinated by conserved residues at the dimer interface, is critical for RNase J dimerization and exonuclease activity. The structures may also shed light on the mechanism of RNase J exo- and endonucleolytic activity switch.
Ferric uptake regulator (Fur) is a transcriptional regulator that controls the expression of genes involved in the uptake of iron and manganese, as well as vital nutrients, and is essential for intracellular redox cycling. We identified a unique Fur homolog (DR0865) from Deinococcus radiodurans, which is known for its extreme resistance to radiation and oxidants. A dr0865 mutant (Mt-0865) showed a higher sensitivity to manganese stress, hydrogen peroxide, gamma irradiation and ultraviolet (UV) irradiation than the wild-type R1 strain. Cellular manganese (Mn) ion (Mn2+) analysis showed that Mn2+, copper (Cu2+), and ferric (Fe3+) ions accumulated significantly in the mutant, which suggests that the dr0865 gene is not only involved in the regulation of Mn2+ homeostasis, but also affects the uptake of other ions. In addition, transcriptome profiles under MnCl2 stress showed that the expression of many genes involved in Mn metabolism was significantly different in the wild-type R1 and DR0865 mutant (Mt-0865). Furthermore, we found that the dr0865 gene serves as a positive regulator of the manganese efflux pump gene mntE (dr1236), and as a negative regulator of Mn ABC transporter genes, such as dr2283, dr2284 and dr2523. Therefore, it plays an important role in maintaining the homoeostasis of intracellular Mn (II), and also other Mn2+, zinc (Zn2+) and Cu2+ ions. Based on its role in manganese homeostasis, DR0865 likely belongs to the Mur sub-family of Fur homolog.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major cause of the global burden of hepatitis. One of the main routes of transmission for both viruses is through exposure to infected blood, which includes sharing blood-contaminated syringes and needles. Human immunodeficiency virus (HIV) attacks the immune system and results in acquired immune deficiency syndrome and opportunistic infections. The objective of this study was to assess the epidemiology of HBV and HCV infections among HIV-infected people who inject drugs (PWID). The study enrolled 100 PWID from different addiction centers of the city of Lahore in Pakistan. All subjects were HIV-infected males and were above 16 years of age. Screening of HBV and HCV infections was performed through immunochromatography tests and enzyme-linked immunosorbent assays. The prevalence of HCV and HBV infections among the 100 HIV-infected PWID was 55% and 6%, respectively. HIV monoinfection was found in 37% of the subjects, while triple infection was detected in 2% of the subjects. Majority of the HIV-infected PWID were using heroin and Avil injections (65%). Half of the subjects had used injection drugs for 1-5 years, while 32% had used injection drugs for 6-10 years. HCV infection was more common than HBV infection among the enrolled subjects. Most of the PWID were practicing heroin and Avil injections.
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