Mechanism for fine regulation of RNA synthesis discovered
29 June 2009
German and US researchers have discovered a new piece in the puzzle
of epigenetics — they have shown that the enzyme TFIIH kinase is
involved in epigenetic regulation.
The discovery was made by Professor Dirk Eick and staff members of
the Institute of Clinical Molecular Biology and Tumor Genetics of
Helmholtz Zentrum München, together with colleagues from the University
of Wisconsin-Madison, Wisconsin, USA.
For many years scientists have known that the numerous biological
functions of an organism are not regulated solely by the DNA sequence of
its genes: Superordinate regulatory mechanisms exist that contribute to
determining the fate of genes.
Although they are not anchored in the DNA, they can even be passed on
to subsequent generations to a certain extent. Intensive research in
recent years has shown that these mechanisms — bundled under the term
epigenetics, are very multifaceted and complex.
The scientists were interested in the fine regulation of the cell
nucleus enzyme RNA polymerase II. This transcribes the genetic
information of the genetic substance DNA into messenger RNA (mRNA)—
which in turn is the basis for protein synthesis.
At the same time RNA polymerase II is also responsible for the
production of other kinds of RNA molecules, the so-called snRNA, which
are not translated into proteins but take on other tasks.
In prior research Eick and his colleagues had observed that a certain
region of the RNA polymerase II enzyme — the carboxy-terminal domain —
is involved in deciding which kinds of RNA are formed. In humans this
domain consists of 52 repeats of a sequence of seven amino acids.
For RNA synthesis the determining factor is whether and how specific
amino acids of this region are modified biochemically. Thus, it is
absolutely essential for the synthesis of snRNA that the amino acid
serine at position 7 of this repeat sequence is provided with an
additional phosphate group.
If this is lacking, mRNA will be produced, but not any snRNA. The
reason for that is presumably that this phosphorylation enables the
interaction with a protein complex — the so-called integrator complex —
which is necessary for snRNA formation. In other words, the modification
of the enzyme RNA polymerase II at defined positions regulates whether
this enzyme can produce certain kinds of RNA molecules or not.
In their latest research, the scientists led by Dirk Eick showed that
the enzyme TFIIH kinase is responsible for the selective phosphorylation
of RNA polymerase II.
“With these findings another building block has been identified that
plays a key role in epigenetic regulation by means of RNA polymerase
II,” Professor Eick said. “This is of great significance because
knowledge of epigenetic mechanisms is necessary in order to better
understand cancer and other diseases and to be able to provide more
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