Curiosity: yeast modified to cause brain abnormalities

• Researchers at Emory University and the University of Texas Health Science Centre found that mutations causing serious developmental disabilities in human babies have similar effects in budding yeast.

• The findings are a significant step in the study of these conditions and suggest that drugs to treat these conditions in yeast could be tested first.

• Pontocerebellar hypoplasia type 1 (PCH1) is a serious medical condition that presents at birth, causing delayed development, diffuse weakness, movement problems, and intellectual disability in babies.

• Four siblings with PCH1 type B were found to carry mutations in a gene called EXOSC3, which encodes one protein of a multiprotein complex in cells called the RNA exosome.

• RNA exosomes, discovered in 1997 in budding yeast, process, monitor, and turnover cellular RNA.

• The study found that different RNA exosomopathy mutations have unique molecular signatures that affect RNA surveillance, ribosome production, and protein synthesis.

• The researchers created a ‘humanised yeast model’ by replacing certain pieces of the yeast RNA exosome with their human or mouse counterparts.

• The model helped identify the precise genetic variants that caused functional defects, including both previously known mutations and new ones.

• The study suggests that future drugs to ameliorate damage in yeast may prove useful in humans as well.