New tool reveals function of enigmatic gene sequences
Date:
March 3, 2022
Source:
Karolinska Institutet
Summary:
While the large proportion of our genome that does not instruct
our cells to form proteins has been harder to study than
protein-coding genes, it has been shown to have vital physiological
functions. Scientists have now developed new high-precision tools
able to identify what these noncoding sequences do. The study may
eventually contribute to the development of new, targeted drugs.
FULL STORY ========================================================================== While the large proportion of our genome that does not instruct our cells
to form proteins has been harder to study than protein-coding genes,
it has been shown to have vital physiological functions. Scientists at Karolinska Institutet in Sweden have now developed new high-precision
tools able to identify what these noncoding sequences do. The study, which
is published in the journal Nature Genetics,may eventually contribute
to the development of new, targeted drugs.
==========================================================================
Only a small proportion of our genome comprises genes that instruct the
cells to make specific proteins; the majority are so-called noncoding
DNA, sometimes called "junk DNA" given that their function has been
largely unknown. However, recent research has shown that some of these sequences can give rise to RNA which affects vital cellular processes. It transpires that most of the genetic changes linked to different diseases
lie in these very noncoding parts of patients' DNA.
"This has come as a great surprise and we now need to understand in
detail how these genetic changes affect different diseases in order to eventually be able to develop more accurate drugs," says the study's first author Per Johnsson, researcher at the Department of Cell and Molecular Biology, Karolinska Institutet. "Generally speaking we don't know that
much about this interaction, but we believe that noncoding RNA will one
day be a source of attractive drug candidates. It's therefore extremely important that we speed up the characterisation of these RNA molecules."
For this study, the researchers combined single-cell sequencing with mathematical calculations to show that it is possible in this way to
identify the function of noncoding RNA, something that has proved very difficult before.
Using these tools, they were then able to identify an entirely
new mechanism for how the RNA molecules regulate the activity of
protein-coding genes in their vicinity.
"After many years of development, single-cell sequencing has now reached
a stage where we can isolate individual cells and study regulating
mechanisms with high precision," says principal investigator Rickard
Sandberg, professor at the Department of Cell and Molecular Biology,
Karolinska Institutet. "This is multidisciplinary research that we believe
will contribute significantly to our basic understanding of cell biology
and that, in the long run, can give us new insights into how cellular
function can be influenced through the agency of small drug substances."
The group has so far used the method to study the function of a handful
of noncoding RNA molecules, but there are thousands of similar molecules waiting to be characterised. They now plan to do similar work on RNA
molecules with a possible role in the development of disease, such
as cancer.
"We'll be applying larger-scale methods to study hundreds to thousands
of similar genes in parallel, thus greatly advancing our understanding
of these interesting RNA molecules," says Dr Johnsson.
The study was financed by the Swedish Research Council, the Knut and
Alice Wallenberg Foundation, the Go"ran Gustafsson Foundation and the
Vallee Foundation.
========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.
========================================================================== Journal Reference:
1. Per Johnsson, Christoph Ziegenhain, Leonard Hartmanis, Gert-Jan
Hendriks,
Michael Hagemann-Jensen, Bjo"rn Reinius, Rickard Sandberg.
Transcriptional kinetics and molecular functions of long noncoding
RNAs.
Nature Genetics, 2022; DOI: 10.1038/s41588-022-01014-1 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220303120801.htm
--- up 3 days, 10 hours, 50 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)