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Research reveals the scale of disorder underpinning Motor Neurone Disease
Overview
Researchers at the Francis Crick Institute and UCL have shown that hundreds of proteins and mRNA molecules are found in the wrong place in nerve cells affected by Motor Neuron Disease (MND), also known as Amyotrophic Lateral Sclerosis (ALS).
New research published in Neuron shows that the problem is much broader. This ‘mislocalization’ affects many more proteins than first thought, especially those involved in RNA binding. The mislocalization extends to mRNAs too, molecules that deliver instructions to make proteins from the DNA in the nucleus.
The researchers used stem cells from patients to create motor neurons with ALS-causing mutations in the TARDBP and VCP genes. They then separated the two main compartments of the cell (nucleus and cytoplasm) and analyzed all the mRNA and protein within each. They found that in ALS cells, hundreds of mRNAs and proteins were mislocated compared to healthy cells.
They observed proteins and mRNAs relocating from the cell’s nucleus (the ‘control center’) into the cytoplasm (the ‘body’ of the cell) or vice versa, hinting at potential transport issues within the cell. The researchers also saw that mislocated mRNAs and proteins interacted more with each other, compared to those in the right place.
Reference: Nucleocytoplasmic mRNA redistribution accompanies RNA binding protein mislocalization in ALS motor neurons and is restored by VCP ATPase inhibition. THE FRANCIS CRICK INSTITUTE
Speakers
Isra Zaman
B.Sc Life Sciences, M.Sc Biotechnology, B.Ed