Certain diseases such as cystic fibrosis and muscular dystrophy are linked to genetic mutations that damage the important biological process of rearranging gene sequences in pre-messenger RNA, a procedure called RNA splicing.
The single-molecule florescence microscope can view individual molecules.
Credit: Diana Hunt
These conditions are difficult to prevent because scientists are still grasping to understand how the splicing process works. Now, researchers from Brandeis University and the University of Massachusetts Medical School have teamed up to unravel a major component in understanding the process of RNA splicing.
In a recent paper published in Cell Press, research specialist Inna Shcherbakova of Brandeis and UMMS, and a team of researchers led by professors Jeff Gelles (Brandeis) and Melissa J. Moore (UMMS), explain how the molecular machine known as the spliceosome begins the process of rearranging gene sequences.
In order to convey instructions for synthesizing protein to the ribosome, RNA — a transcribed copy of DNA — must be translated into mRNA. Part of the process of translating pre-messenger RNA into mRNA involves cutting out gene segments that don't contain information relevant to protein synthesis, called introns, and connecting the remaining pieces together.
The spliceosome does the genetic cutting and pasting. It is a complicated complex, made up of four major parts and more than 100 accessory proteins that come together and break apart throughout the splicing process. Think of the spliceosome as an old Transformers robot — it has individual pieces that operate independently but can also come together to form a larger structure.
Sometimes, such as in the case of cystic fibrosis, a mutation will cause the spliceosome to snip in the wrong place, cutting out important sequences instead of introns, and resulting in the production of a faulty protein.
In studying the Transformer-like spliceosome, researchers have been unable to reconcile how the different components of the complex coordinate. To initiate the splicing process, two pieces of the spliceosome bind to the two ends of an intron. Until now, scientists believed this to be highly ordered process: first Part 1 bound, and then it would somehow tell Part 2 to attach.
In a highly ordered process in primitive organisms such as yeast, the introns are small and it's easy for Part 1 and Part 2 to communicate. But how would that process work in humans, where introns are made up of thousands of nucleotides? How could the two parts — which jumpstart the whole splicing process — communicate?
To find out, Shcherbakova aimed a single-molecule florescence microscope built in the Gelles lab at the spliceosome. By tagging the different parts of the complex with fluorescent colors, the team discovered that the process is more flexible than scientists imagined.
The two first major components of the spliceosome do not need to communicate with one another to start the splicing process, nor does it matter which piece attaches to the gene first. Either of the components, called U1 and U2, can attach first and the process works equally well.
"The process is much more sensible than we originally thought," Gelles says.
Now that scientists understand how the major components of splicing can come together, they can study how the different steps of the process are orchestrated.
"We are just scratching the surface in understanding this process, but ultimately, we hope to understand how this process goes wrong and how it can be fixed," Gelles says.
Leah Burrows | EurekAlert!
'Lipid asymmetry' plays key role in activating immune cells
20.02.2018 | Biophysical Society
New printing technique uses cells and molecules to recreate biological structures
20.02.2018 | Queen Mary University of London
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
20.02.2018 | Life Sciences
20.02.2018 | Medical Engineering
20.02.2018 | Physics and Astronomy