tRNA methylation: On the role of modified nucleosides in transfer-RNA

Author(s):  
Helga Kersten
2019 ◽  
Vol 5 (12) ◽  
pp. eaax8030 ◽  
Author(s):  
Bee-Zen Peng ◽  
Lars V. Bock ◽  
Riccardo Belardinelli ◽  
Frank Peske ◽  
Helmut Grubmüller ◽  
...  

During translation, the ribosome moves along the mRNA one codon at a time with the help of elongation factor G (EF-G). Spontaneous changes in the translational reading frame are extremely rare, yet how the precise triplet-wise step is maintained is not clear. Here, we show that the ribosome is prone to spontaneous frameshifting on mRNA slippery sequences, whereas EF-G restricts frameshifting. EF-G helps to maintain the mRNA reading frame by guiding the A-site transfer RNA during translocation due to specific interactions with the tip of EF-G domain 4. Furthermore, EF-G accelerates ribosome rearrangements that restore the ribosome’s control over the codon-anticodon interaction at the end of the movement. Our data explain how the mRNA reading frame is maintained during translation.


Biochimie ◽  
1995 ◽  
Vol 77 (1-2) ◽  
pp. 139-141 ◽  
Author(s):  
H. Grosjean ◽  
M. Sprinzl ◽  
S. Steinberg

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.


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