Nav: Home

Structural and biochemical studies clarify the methylation mechanism of anticodon in tRNA

November 06, 2019

Genetic information on DNA is transcribed onto messenger RNA and then is decoded by transfer RNA (tRNA) during protein synthesis. The methylation of ribose of the first position of anticodon (position 34 in tRNA) is commonly observed in tRNAs from three domains of life. This methylation reinforces the codon-anticodon interaction and prevents errors during protein synthesis. We knew that eukaryote, a protein complex between Trm7 and Trm734 (Trm7-Trm734), is the responsible tRNA methyltransferase for this methylation. However, important questions remained. For example, why does Trm7-Trm734 act only on specific tRNA?, and why is Trm734 required for the methylation at position 34 in tRNA? To address these issues, a group at Ehime University (Akira Hirata, Keisuke Okada, Kazunori Yoshii, Hiroyuki Shiraishi and Hiroyuki Hori) working with a group at KEK (Shinya Saijo, Kento Yonezawa and Nobutaka Shimizu) solved the crystal structure of Trm7-Trm734 and measured a small angle X-ray scattering. Based on these structural studies, they performed biochemical studies. Their findings are as follows: Trm7-Trm734 preferentially methylates tRNA transcript variants possessing two of three factors (Cm32, m1G37 and pyrirmidine34). Therefore, tRNAPhe, tRNATrp and tRNALeu are specifically methylated by Trm7-Trm734. Trm7 possesses a Rossmann-fold catalytic domain, while Trm734 consists of three WD40 ?-propeller domains (termed BPA, BPB and BPC). BPA and BPC form a unique V-shaped cleft, which docks with Trm7. Small angle X-ray scattering reveals that Trm7-Trm734 exists as a hetero-dimer in solution and Trm734 is required for the positioning of tRNA for methylation.

It has long been a mystery as to why Trm7-Trm734 acts only on specific tRNAs. The study explains the tRNA recognition mechanism of Trm7-Trm734 and clarifies the roles of the subunits. In humans, the defect of methylation at the first position of anticodon in tRNA causes nosyndromic X-linked intellectual disability. Therefore, this study contributes to the understanding of genetic defects and developments in genetic diagnosis and gene therapy.
The synchrotron radiation experiments were performed at the BL26B1, BL38B1 and BL45XU in the SPring-8 with the approval of the Japan Synchrotron Radiation Research Institute (JASRI) (Proposal No. 2013B1272, 2014A1246, 2014B1063, 2015B2047 and 2016A2547), and at the BL-10C in the Photon Factory with the support of the Platform for Drug Discovery, Informatics, and Structural Life Science (PDIS) from Japan Agency for Medical Research and Development (AMED). This research was partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research [Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from AMED under Grant Number JP19am0101071 (support number 0997). Furthermore, the authors thank the Division of Material Science and Applied Protein Research of the Advanced Research Support Center, Ehime University for the Typhoon FLA 7000 system.

Ehime University

Related Methylation Articles:

Oncotarget: DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques
Oncotarget Volume 11, Issue 10 reported that the statistically associated Cp G sites were analyzed in blood samples from two separate atherothrombotic stroke cohorts, ischemic stroke-cohort 1: 37 atherothrombotic patients and 6 controls, ischemic stroke-cohort 2: 80 atherothrombotic patients and 184 controls.
Stressed corals set up progeny for a better life
First evidence that animal DNA methylation patterns can be passed to the next generation.
RNA modification -- Methylation and mopping up
Ludwig-Maximilian-Universitaet (LMU) in Munich researchers have discovered a novel type of chemical modification in bacterial RNAs.
Structural and biochemical studies clarify the methylation mechanism of anticodon in tRNA
Groups in Ehime University, Japan and the High Energy Accelerator Research Organization (KEK), Japan have solved the crystal structure of the eukaryotic Trm7-TRm734 complex, which methylates the ribose at the first position of anticodon in tRNA.
First glimpse at what ancient Denisovans may have looked like, using DNA methylation data
Exactly what our ancient Denisovan relatives might have looked like had been anyone's guess for a simple reason: the entire collection of Denisovan remains includes a pinky bone, three teeth, and a lower jaw.
Methylation of microRNA may be a new powerful biomarker for cancer
Researchers from Osaka University found that levels of methylated microRNA were significantly higher in tissue and serum from cancer patients compared with that from normal controls.
DNA methylation-based estimator of telomere length
Leukocyte DNAm TL is applicable across the entire age spectrum and is more strongly associated with age than measured leukocyte TL.
Scientists uncover mystery of DNA methylation
To a large extent, DNA methylation, which regulates vital cell functions, is still a big mystery to the scientific world.
Study finds fish preserve DNA 'memories' far better than humans
We are all familiar with the common myth that fish have poor memory, but it turns that their DNA has the capacity to hold much more memory than that of humans.
TET proteins: double agents in DNA methylation prevent catastrophic cancer
In their latest study, published in this week's online issue of Proceedings of the National Academy of Sciences, researchers at La Jolla Institute for Immunology (LJI), reveal how the finely tuned balance between DNA methylation and demethylation prevents genomic instability and cancer.
More Methylation News and Methylation Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 3: Shared Immunity
More than a million people have caught Covid-19, and tens of thousands have died. But thousands more have survived and recovered. A week or so ago (aka, what feels like ten years in corona time) producer Molly Webster learned that many of those survivors possess a kind of superpower: antibodies trained to fight the virus. Not only that, they might be able to pass this power on to the people who are sick with corona, and still in the fight. Today we have the story of an experimental treatment that's popping up all over the country: convalescent plasma transfusion, a century-old procedure that some say may become one of our best weapons against this devastating, new disease.   If you have recovered from Covid-19 and want to donate plasma, national and local donation registries are gearing up to collect blood.  To sign up with the American Red Cross, a national organization that works in local communities, head here.  To find out more about the The National COVID-19 Convalescent Plasma Project, which we spoke about in our episode, including information on clinical trials or plasma donation projects in your community, go here.  And if you are in the greater New York City area, and want to donate convalescent plasma, head over to the New York Blood Center to sign up. Or, register with specific NYC hospitals here.   If you are sick with Covid-19, and are interested in participating in a clinical trial, or are looking for a plasma donor match, check in with your local hospital, university, or blood center for more; you can also find more information on trials at The National COVID-19 Convalescent Plasma Project. And lastly, Tatiana Prowell's tweet that tipped us off is here. This episode was reported by Molly Webster and produced by Pat Walters. Special thanks to Drs. Evan Bloch and Tim Byun, as well as the Albert Einstein College of Medicine.  Support Radiolab today at