Nav: Home

New sequencing technology will help scientists decipher disease mechanisms

July 02, 2020

New technologies capable of sequencing single molecules in fine detail will help scientists better understand the mechanisms of rare nucleotides thought to play an important role in the progression of some diseases.

A review paper, led by a scientist at the University of Birmingham, describes how emerging sequencing technologies will transform our understanding of these molecules, ultimately leading to new drug targets. The paper is published in the journal Trends in Biotechnology.

Expression of genes to make protein involves making a messenger RNA molecule. Although RNA, like DNA consist of the four nucleotides, some of them carry decorations called the epitranscriptome. These modified nucleotides are important additions to the genetic code whose functions are little understood, but have been linked to disease such as obesity, cancer and neurological disorders.

Although the importance of the epitranscriptome is recognized, its detection is difficult and comes with high error rates.

Scientist have been interested in these rare modified nucleotides since their discovery more than 40 years ago, but they had been very difficult to examine in specific genes due to technical difficulties. However, their importance has been recognized, because many human parasites and viruses have them. Even more, some viruses including coronavirus SARS-CoV2 have their own RNA modification enzymes, originally acquired from their hosts, but then adapted to their needs.

Until recently, the study of these modified nucleotides has been limited because they occur so rarely, and existing technologies have not been sufficiently fine-tuned to detect the modifications.

The new technology, developed by Oxford Nanopore Technologies, is promising to overcome current sequencing limitations, with highly selective sequencing capabilities. By identifying specific nucleotide targets associated with particular diseases, drug developers will be able to start to investigate inhibitor drugs that can interfere with the molecules and influence the progression of the disease.

Lead author of this multinational study, Dr Matthias Soller from the University of Birmingham, UK, says: "These modified nucleotides are particularly hard to detect and previously it was impossible to examine their occurrence in the entire genome with high confidence".

First author and Schmidt Science Fellow Dr Ina Anreiter, University of Toronto, Canada, adds: "Previously, it was only possible to look at one modification at a time, but there a more than just one and they likely hiding a yet to discover code.

"This new technology will really enable a step-change in how we approach modified nucleotides, giving us a 'real-time' topographic map of where the molecules are within the genome, and how frequently they occur. This will be really important in instructing further research into their function and providing us with new insights into how these molecules lead to human disease."

Dr Soller added: "There is plenty of work still to be done to further develop these sequencing devices, including improving the machine-learning capability for interpreting the sequencing signals, but progress is happening rapidly and I think we will be seeing some very exciting results emerging from this technology."
Co-author, Dr. Sarath Janga from Indiana University, USA says: "SARS-CoV2 RNA virus responsible for the COVID19 pandemic has about 40 RNA modifications and it is already clear, that they are essential for the virus. Hence, understanding their function in virus replication will provide new directions for combating viral infections"

Notes to editor:

* The University of Birmingham is ranked amongst the world's top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 6,500 international students from over 150 countries.

* Soller et al (2020). 'New twists on detecting mRNA modification dynamics'. Trends in Biotechnology.

University of Birmingham

Related Rna Articles:

RNA as a future cure for hereditary diseases
ETH Zurich scientists have developed an RNA molecule that can be used in bone marrow cells to correct genetic errors that affect protein production.
Bringing RNA into genomics
By studying RNA-binding proteins, a research consortium known as ENCODE (Encyclopedia of DNA Elements) has identified genomic sites that appear to code for RNA molecules that influence gene expression.
RNA key in helping stem cells know what to become
If every cell has the same genetic blueprint, why does an eye cell look and act so differently than a brain cell or skin cell?
RNA structures by the thousands
Researchers from Bochum and Münster have developed a new method to determine the structures of all RNA molecules in a bacterial cell at once.
New kind of CRISPR technology to target RNA, including RNA viruses like coronavirus
Researchers in the lab of Neville Sanjana, PhD, at the New York Genome Center and New York University have developed a new kind of CRISPR screen technology to target RNA.
Discovery of entirely new class of RNA caps in bacteria
The group of Dr. Hana Cahová of the Institute of Organic Chemistry and Biochemistry of the CAS, in collaboration with scientists from the Institute of Microbiology of the CAS, has discovered an entirely new class of dinucleoside polyphosphate 5'RNA caps in bacteria and described the function of alarmones and their mechanism of function.
New RNA mapping technique shows how RNA interacts with chromatin in the genome
A group led by scientists from the RIKEN Center for Integrative Medical Sciences (IMS) in Japan have developed a new method, RADICL-seq, which allows scientists to better understand how RNA interacts with the genome through chromatin--the structure in which the genome is organized.
Characterising RNA alterations in cancer
The largest and most comprehensive catalogue of cancer-specific RNA alterations reveals new insights into the cancer genome.
A new approach to reveal the multiple structures of RNA
The key of the extraordinary functionality of ribonucleic acid, better known as RNA, is a highly flexible and dynamic structure.
RNA modification -- Methylation and mopping up
Ludwig-Maximilian-Universitaet (LMU) in Munich researchers have discovered a novel type of chemical modification in bacterial RNAs.
More RNA News and RNA 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

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at     You can read The Transition Integrity Project's report here.