Mutant HSPB1 causes loss of translational repression by binding to PCBP1, an RNA binding protein with a possible role in neurodegenerative disease.
Thomas Geuens (pictured left) from Timmerman lab characterized mutations in the small heat shock proteins HSPB1 and HSPB8 which have been found to cause axonal variants of inherited peripheral neuropathies. His efforts led to two manuscripts published beginning of 2017.
Geuens and colleagues show that mutant HSPB1 binds the RNA binding protein PCBP1 which negatively affects the translational repressive activity of PCBP1. RNA immunoprecipitation coupled to RNA sequencing showed that PCBP1 binds mRNA of several known genes associated with hereditary peripheral neuropathies and hereditary spastic paraplegias.
In addition, functional studies performed on 5 novel HSPB1 and 3 novel HSPB8 mutations further demonstrate the pleiotropic character of these small heat shock proteins.
Mutant HSPB1 causes loss of translational repression by binding to PCBP1, an RNA binding protein with a possible role in neurodegenerative disease. - dx.doi.org/10.1186/s40478-016-0407-3
Axonal Neuropathies due to Mutations in Small Heat Shock Proteins: Clinical, Genetic, and Functional Insights into Novel Mutations. - dx.doi.org/10.1002/humu.23189
Welcome to Neuromics, a research project funded by the European Commission for five years.
In reality, so-called rare diseases are anything but rare. 6-8% of the European population – between 27 and 36 million people – are affected by one of the 5000-8000 distinct rare diseases.
Neuromics studies 10 rare neurodegenerative and neuromuscular diseases...read more
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