New sequencing technology will help scientists decipher disease
mechanisms

Date:
July 2, 2020
Source:
University of Birmingham
Summary:
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.



FULL STORY ==========================================================================
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."

========================================================================== Story Source: Materials provided by University_of_Birmingham. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Ina Anreiter, Quoseena Mir, Jared T. Simpson, Sarath C. Janga,
Matthias
Soller. New Twists in Detecting mRNA Modification Dynamics. Trends
in Biotechnology, 2020; DOI: 10.1016/j.tibtech.2020.06.002 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200702115032.htm

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