Blueprint for proteins: How mRNA gets its final shape

Date:
February 21, 2022
Source:
Martin-Luther-Universita"t Halle-Wittenberg
Summary:
Proteins need to interact in a complex manner for a so-called
'messenger RNA' (mRNA) to be created in human cells from a precursor
molecule. mRNA provides a blueprint for proteins; the first vaccines
against the coronavirus are also based on mRNAs. Scientists have
now discovered how an essential final step in the production of
mRNA precisely works.



FULL STORY ========================================================================== Proteins need to interact in a complex manner for a so-called
"messenger RNA" (mRNA) to be created in human cells from a precursor
molecule. mRNA provides a blueprint for proteins; the first vaccines
against the coronavirus are also based on mRNAs. A team from Martin
Luther University Halle-Wittenberg (MLU) and the Max Planck Institute
(MPI) of Biochemistry in Martinsried has discovered how an essential
final step in the production of mRNA precisely works. The study was
published in Genes & Development.


========================================================================== Proteins are responsible for all of the body's essential processes. In
a sense, the genes in the human genome act as building instructions for
them. However, an intermediate step is necessary before new proteins can
be created: "First the DNA must be transcribed: A chain-like precursor
RNA is produced which is an exact copy of the DNA. From this, several
steps are required to create the mature mRNA. This process is essential
for the cell to build new proteins," says biochemist Professor Elmar
Wahle from MLU who led the team alongside Professor Elena Conti, an
expert in structural biology at the MPI of Biochemistry.

There is no room for error in this complicated process -- even the
smallest changes in the structure of a protein can impair its function and
lead to the development of diseases. "The mRNA not only determines the structure of a protein, but also how much of it is produced. Therefore,
it is important that its structure is also precisely controlled," Wahle
adds. The proteins involved in reading out and transcribing DNA into
precursor RNA are already known to scientists. However, an important
sub-step in the process of creating mature mRNA has only been vaguely understood until now. First, the chains of the mRNA precursors are
cleaved at a specific point to create uniform products. Then, a long
molecular chain, the so-called poly(A) tail, is attached to one end of
the strand. This ensures that the mRNA is not directly degraded again
in the cells, and it is also important for protein synthesis.

The researchers from Halle and Martinsried joined forces to investigate
these final steps in the production of mRNA more closely. To do this,
the team from MLU first recreated the process in a test tube. The
scientists had to pick the right proteins from a pool of 80 possible candidates. Those had to be mixed with the precursor RNA in a correct
ratio before both reactions could take place. The researchers at MPI
studied the process in more detail using cryo- electron microscopy. "We basically reproduced the conditions in a normal cell, although the
natural process is probably even more complex," explains Wahle.

Sixteen proteins are involved in creating the final molecules. "The
process is universal, affecting every cell and every mRNA molecule in
the body," says Felix Sandmeir from the MPI of Biochemistry.

On a side note, the process used to produce the Pfizer/Biontech and
Moderna vaccines is much simpler: "The mRNA is created according to the
same principle, but in contrast to the human cell, very simple enzymes
are used and the complicated conversion of a precursor into the mature
mRNA can be avoided," says Wahle in conclusion.

The study was funded in part by the Deutsche Forschungsgemeinschaft
(DFG, German Research Foundation).

========================================================================== Story Source: Materials provided by Martin-Luther-Universita"t_Halle-Wittenberg. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Moritz Schmidt, Florian Kluge, Felix Sandmeir, Uwe Ku"hn, Peter
Scha"fer,
Christian Tu"ting, Christian Ihling, Elena Conti, Elmar Wahle.

Reconstitution of 3' end processing of mammalian pre-mRNA reveals
a central role of RBBP6. Genes & Development, 2022; DOI: 10.1101/
gad.349217.121 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220221085735.htm

--- up 11 weeks, 2 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)