scholarly journals Role of Modified Nucleosides in the Translation Function of tRNAs from Extreme Thermophilic Bacteria and Animal Mitochondria

2007 ◽  
Vol 80 (7) ◽  
pp. 1253-1267 ◽  
Author(s):  
Kimitsuna Watanabe
Author(s):  
Darya B. Nizheharodava ◽  
Marina M. Zafranskaya ◽  
Eugenii I. Kvasyuk ◽  
Aliaksei G. Sysa

Taking into account the special role of oxidative stress that increases during cancer chemotherapy, the effect of the antioxidant emoxipine on peripheral blood mononuclears was studied under conditions that simulate the cytotoxic effects of antimetabolites of a number of modified cytidine nucleosides in relation to the tumor cell line K562. Lymphoid cells were also a source for subsequent modelling of the immune response to the cancer. It was found that neither the modified nucleosides themselves nor their combination with emoxipine caused changes in IL-2-stimulated cytotoxicity of lymphoid cells in relation to K562 tumor cell line. A study of the expression of the CD107a marker showed a significant stimulating effect of 1 µmol/L of citarabine on the activation of subpopulations of T-lymphocytes (CD3+ ) and cytotoxic T-lymphocytes (CD3+ CD8+ ).


2020 ◽  
Author(s):  
Akiko Ogawa ◽  
Chisae Nagiri ◽  
Wataru Shihoya ◽  
Asuka Inoue ◽  
Kouki Kawakami ◽  
...  

SUMMARYAbout 150 post-transcriptional RNA modifications have been identified in all kingdoms of life. During RNA catabolism, most modified nucleosides are resistant to degradation and are released into the extracellular space. In this study, we explored the physiological role of these extracellular modified nucleosides and found that N6-methyladenosine (m6A), widely known as an epigenetic mark in RNA, acts as a ligand for the adenosine A3 receptor, for which it has greater affinity than unmodified adenosine. Structural modeling defined the amino acids required for specific binding of m6A to the A3 receptor. m6A is dynamically released in response to cytotoxic stimuli and facilitates type I allergy. Our findings shed light on m6A as a signaling molecule with the ability to activate GPCRs, a previously unreported property of RNA modifications.


2018 ◽  
Vol 19 (12) ◽  
pp. 4080 ◽  
Author(s):  
Chie Tomikawa

More than 90 different modified nucleosides have been identified in tRNA. Among the tRNA modifications, the 7-methylguanosine (m7G) modification is found widely in eubacteria, eukaryotes, and a few archaea. In most cases, the m7G modification occurs at position 46 in the variable region and is a product of tRNA (m7G46) methyltransferase. The m7G46 modification forms a tertiary base pair with C13-G22, and stabilizes the tRNA structure. A reaction mechanism for eubacterial tRNA m7G methyltransferase has been proposed based on the results of biochemical, bioinformatic, and structural studies. However, an experimentally determined mechanism of methyl-transfer remains to be ascertained. The physiological functions of m7G46 in tRNA have started to be determined over the past decade. For example, tRNA m7G46 or tRNA (m7G46) methyltransferase controls the amount of other tRNA modifications in thermophilic bacteria, contributes to the pathogenic infectivity, and is also associated with several diseases. In this review, information of tRNA m7G modifications and tRNA m7G methyltransferases is summarized and the differences in reaction mechanism between tRNA m7G methyltransferase and rRNA or mRNA m7G methylation enzyme are discussed.


3 Biotech ◽  
2019 ◽  
Vol 9 (3) ◽  
Author(s):  
Punniyakotti Elumalai ◽  
Punniyakotti Parthipan ◽  
Jayaraman Narenkumar ◽  
Balakrishnan Anandakumar ◽  
Jagannathan Madhavan ◽  
...  

1998 ◽  
Vol 180 (11) ◽  
pp. 2883-2888 ◽  
Author(s):  
Kathleen R. Noon ◽  
Eveline Bruenger ◽  
James A. McCloskey

ABSTRACT Posttranscriptional modification is common to many types of RNA, but the majority of information concerning structure and function of modification is derived principally from tRNA. By contrast, less is known about modification in rRNA in spite of accumulating evidence for its direct participation in translation. The structural identities and approximate molar levels of modifications have been established for 16S and 23S rRNAs of the archaeal hyperthermophile Sulfolobus solfactaricus by using combined chromatography-mass spectrometry-based methods. Modification levels are exceptionally high for prokaryotic organisms, with approximately 38 modified sites in 16S rRNA and 50 in 23S rRNA for cells cultured at 75°C, compared with 11 and 23 sites, respectively, in Escherichia coli. We structurally characterized 10 different modified nucleosides in 16S rRNA, 64% (24 residues) of which are methylated at O-2′ of ribose, and 8 modified species in 23S rRNA, 86% (43 residues) of which are ribose methylated, a form of modification shown in earlier studies to enhance stability of the polynucleotide chain. From cultures grown at progressively higher temperatures, 60, 75, and 83°C, a slight trend toward increased ribose methylation levels was observed, with greatest net changes over the 23°C range shown for 2′-O-methyladenosine in 16S rRNA (21% increase) and for 2′-O-methylcytidine (24%) and 2′-O-methylguanosine (22%) in 23S rRNA. These findings are discussed in terms of the potential role of modification in stabilization of rRNA in the thermal environment.


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