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Decaying RNA molecules tell a story
Heidelberg, 4 June 2015 – Once messenger RNA (mRNA)
has done its job – conveying the information to produce
the proteins necessary for a cell to function – it is no longer
required and is degraded. Scientists have long thought that the
decay started after translation was complete and that decaying
RNA molecules provided little biological information.
Now a team from EMBL Heidelberg and Stanford University
led by Lars Steinmetz has turned this on its head. The
researchers have shown that one end of the mRNA begins to
decay while the other is still serving as a template for protein
production. Thus, studying the decaying mRNA also provides
a snapshot of how proteins are produced.
The discovery was made almost by accident. As part of research
into how DNA is transcribed into mRNA, co-researchers
Vicent Pelechano and Wu Wei developed an in vivo method
to count decaying mRNA molecules in the cell. mRNA has a
protective ‘cap’ that prevents it from being degraded – once
that cap is removed, the decay begins. The researchers spotted
a pattern in the distribution of the ‘cap-less’ RNA that they
didn’t expect.
Vicent Pelechano, from the Steinmetz group at EMBL
Heidelberg, explains: “The decaying RNA was thought to be
of little interest biologically, so we were really surprised to see
a pattern. We looked more deeply into it because it appeared
to be linked to the genetic code, but we never expected it to
lead to a completely new understanding of how mRNA and
ribosomes interact.”
Proteins are produced from mRNA by ribosomes – ‘molecular
machines’ that pass successively along the mRNA to translate
its nucleotides into amino acids. It was thought that the mRNA
only started to decay once the final ribosome had left it and
translation was complete. In fact, the researchers were able to
determine that the protective ‘cap’ is removed and degradation
begins even while ribosomes are still associated with the
mRNA.
They demonstrated that the enzyme degrading mRNA follows
closely behind the ribosome, pausing at set points along the
mRNA, usually after each group of 3 nucleotides, the section of
code that relates to one amino acid. The team believes that this
shows the enzyme pausing while translation goes on – allowing
the ribosome to do its work and move on – before starting to
degrade the mRNA previously protected by the ribosome.
The enzyme that degrades messenger RNA follows the ribosomes and stops
every 3 nucleotides. IMAGE: V.Pelechano/EMBL
• Translation and degradation occur in parallel on the same
mRNA molecule
• The enzyme responsible for mRNA decay appears to
‘wait’ until each amino acid is added before degrading the
template
• New drug-free approach offers a more accurate method to
study ribosomal activity
This novel approach also opens up new avenues to study
ribosomes. “Researchers studying ribosome activity usually
use drugs to stall the ribosomes in place. This can alter the
way we perceive their activity. We are simply looking for the
molecules remaining from mRNA decay and determining
their distribution. We believe this shows a more accurate
picture of what is happening to the mRNA and the ribosome
than was previously possible,” explains Wu Wei of Stanford
University.
Source Article
Pelechano et al. Cell, 4 June 2015 . DOI: 10.1016/j.cell.2015.05.008
Contact:
Isabelle Kling, EMBL Communication Officer, Heidelberg, Germany, Tel: +49 6221 387 8355, www.embl.org, [email protected]
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