Structure of genetic messenger molecules reveals key role in diseases
19 March 2015
Messenger RNAs (mRNA) are linear molecules that contain instructions for producing the proteins that keep living cells functioning. A new study by UCL researchers has shown how the three-dimensional structures of mRNAs determine their stability and efficiency inside cells. This new knowledge could help to explain how seemingly minor mutations that alter mRNA structure might cause things to go wrong in neurodegenerative diseases like Alzheimer’s.
mRNAs carry genetic information from DNA to be translated into proteins. They are generated as long chains of molecules, but they fold up into complex structures by making connections between different sections of the chain. Despite the importance of these structures to how mRNAs function, very little was known about them until now.
The study published in Nature reports a new technique allowing scientists to identify connections that hook sections of an mRNA together.
Further investigation showed that these connections affect how mRNAs interact with other molecules inside cells, and so influence how much protein they eventually produce.
A particularly important connection is found in an mRNA that codes for a
protein called X-box binding protein 1.
Genetic mutations in mRNAs can lead to faulty connections and cause the wrong amounts of protein to be produced. This suggests that a wide range of human diseases could be caused by such mutations.
has great potential!" adds Professor Ule. "Because
understanding the genetic cause is the first step towards finding new
treat these diseases".
The study was supported by the Medical Research Council, Cancer Research UK and the Wellcome Trust.
- Yoichiro Sugimoto, Alessandra Vigilante, Elodie Darbo, Alexandra Zirra, Cristina Militti, Andrea D’Ambrogio, Nicholas M. Luscombe, & Jernej Ule. hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1. Nature (2015) doi:10.1038/nature14280, Published online 18 March 2015
- Professor Jernej Ule's academic profile on Iris
- Professor Nicholas Luscombe's academic profile on Iris
- UCL Genetics Institute
- UCL Brain Sciences
of connections across mRNA molecules, where colour indicates length