FRANKFURT. Even
more detailed insights into the cell will be possible in future with the help
of a new development in which 51猎奇 was involved: Together with
scientists from Israel, the research group led by Professor Harald Schwalbe has
succeeded in accelerating a hundred thousand-fold the nuclear magnetic
resonance (NMR) method for investigating RNA.
In the same way that a single piece of a
puzzle fits into the whole, the molecule hypoxanthine binds to a ribonucleic
acid (RNA) chain, which then changes its three-dimensional shape within a
second and in so doing triggers new processes in the cell. Thanks to an
improved method, researchers are now able to follow almost inconceivably tiny
structural changes in cells as they progress 鈥� both in terms of time as well as
space. The research group led by Professor Harald Schwalbe from the Center for
Biomolecular Magnetic Resonance (BMRZ) at 51猎奇 has succeeded,
together with researchers from Israel, in accelerating a hundred thousand-fold the
nuclear magnetic resonance (NMR) method for investigating RNA.
鈥淭his allows us for the first time to
follow the dynamics of structural changes in RNA at the same speed as they
occur in the cell,鈥� says Schwalbe, describing this scientific breakthrough, and
stresses: 鈥淭he team headed by Lucio Frydman from the Weizmann Institute in
Israel made an important contribution here.鈥�
The new types of NMR experiments use water
molecules whose atoms can be followed in a magnetic field. Schwalbe and his
team produce hyperpolarized water. To do so, they add a compound to the water
which has permanently unpaired electron radicals. The electrons can be aligned
in the magnetic field through excitation with a microwave at -271掳C. This
unnatural alignment produces a polarization which is transferred at +36掳C to
the polarization of the hydrogen atoms used in the NMR. Water molecules
polarized in this way are heated in a few milliseconds and transfered, together
with hypoxanthine, to the RNA chain. The new approach can in general be applied
to observe fast chemical reactions and refolding changes in biomolecules at
atomic level.
In particular the imino groups in RNA can
be closely analyzed using this method. In this way, the researchers were able
to measure structural changes in RNA very accurately. They followed a small
piece of RNA from Bacillus subtilis, which changes its structure during
hypoxanthine binding. This structural change is part of the regulation of the transcription
process, in which RNA is being made from DNA. Such small changes at molecular
level steer a large number of processes not only in bacteria but also in
multicellular organisms and even humans.
This improved method will in future make
it possible to follow RNA refolding in real time 鈥� even if it needs less than a
second. This is possible under physiological conditions, that is, in a liquid
environment and with a natural molecule concentration at temperatures around 36
掳C. 鈥淭he next step will now be not only to study single RNAs but hundreds of
them, in order to identify the biologically important differences in their refolding
rates,鈥� says Boris F眉rtig from Schwalbe鈥檚 research group.
Publication: Mihajlo Novakovic, Gregory L. Olsen, Gy枚rgy Pint茅r, Daniel Hymon, Boris
F眉rtig, Harald Schwalbe, Lucio Frydman: A 300-fold enhancement of imino nucleic
acid resonances by hyperpolarized water provides a new window for probing RNA
refolding by 1D and 2D NMR, PNAS, 16 January 2020
A
picture can be downloaded from:
Caption: Frankfurt researchers followed the movements of this tiny molecule 鈥�
just two-thousandths of the thickness of a piece of paper. The RNA aptamer changes
its structure when it binds hypoxanthine. The green nucleobases change shape
particularly quickly, the ones coloured blue more slowly. The grey regions do
not change.
Further
information: Professor Harald Schwalbe, Center for
Biomolecular Magnetic Resonance (BMRZ),
http://www.bmrz.de/, Institute of Organic Chemistry and Chemical Biology, Riedberg
Campus, Tel.: +49(0)69-798-29737 or -40258, e-mail:
schwalbe@nmr.uni-frankfurt.de.
