The curious case of the yeast modified to develop brain defects Premium

Researchers find mutations causing developmental disabilities in humans have similar effects in yeast, aiding drug testing and understanding conditions.

Researchers at Emory University and the University of Texas Health Science Centre, both in the US, have found that a class of mutations that leads to serious developmental disabilities in human babies has similar effects in budding yeast, a simpler organism. The findings represent a major step in the study of these conditions because they throw light on how they ought to be studied.

Since yeast is easy to study in labs, they also raise the possibility of quickly testing drugs to treat these conditions in yeast first.

Pontocerebellar hypoplasia type 1 (PCH1) is a serious medical condition that presents at birth. Babies born with it have impaired development of two brain regions, the pons and the cerebellum. PCH1 patients show delayed development, diffuse weakness, problems with movement, and intellectual disability. Most don’t survive beyond infancy or early childhood.

In 2012, four siblings with PCH1 type B were all found to carry mutations in a gene called EXOSC3, which encodes one protein of a multiprotein complex in cells called the RNA exosome. This provided the first example of a human disease caused by mutations affecting the RNA exosome. 

The RNA exosome was discovered in 1997 in budding yeast (Saccharomyces cerevisiae). Its primary job is to process, monitor, and turnover cellular RNA.

Subsequent studies of patients with other neurological and developmental disorders uncovered mutations in many other genes related to RNA exosome proteins. These conditions are together called RNA exosomopathies.

Most RNA exosomopathies lead to brain maldevelopment. A major question in the study of these proteins is which exosomopathies lead to which form of maldevelopment.