Yeast colonies grow on agar plates. |Photo source: Rainis Venta (CC BY-SA)
Researchers at Emory University and the University of Texas Health Science Center have both found that a class of mutations that cause severe developmental disorders in human infants have similar effects on budding yeasts in simpler organisms. These findings represent an important step in studying these conditions, as they illuminate how they should be studied.
Because yeasts are easy to study in the lab, they also increase the possibility of quickly testing drugs to treat these diseases in yeast first.
RNA exosomal disease
Pontocerebellar incomplete development type 1 (PCH1) is a serious medical condition that occurs at birth. The baby with it suffers from the development of two brain regions, namely PON and Cerebellum. PCH1 patients exhibit delayed development, diffuse weaknesses, motor problems and intellectual disabilities. Most people cannot survive in infancy or early childhood.
In 2012, four siblings with PCH1 type B were found to carry mutations in a gene called exosc3it encodes a protein that is a polyprotein complex in cells called RNA exosomes. This provides the first example of a human disease caused by mutations influencing RNA exosomes.
RNA exosomes were found in germinated yeast in 1997 (Saccharomyces cerevisiae). Its main job is to process, monitor and operate transgender cellular RNA.
Subsequent studies of other patients with neurological and developmental disorders have found mutations in many other genes associated with RNA exosome proteins. These diseases are called RNA exosomal diseases.
Most extraRNA fibroids cause cerebral malaria. A major question in these protein studies is what exosomal diseases cause which form of malt structure.
RNA exosomes
New Discovery was reported in two papers in April this year, one of which is a journal RNA anotherG3 genomic genetics.
RNA molecules are working copies of genes in our cells. The main copy is DNA. The cells use DNA sequences corresponding to the gene as templates to make the RNA of the gene, and then use RNA to make the protein. Many newly made RNAs were processed before RNA exosomes could play the role of cellularity.
Most RNA in cells is rRNA (ribosomal RNA). Other types are mRNA (Messenger RNA), TRNA (transfer RNA), and various non-coding RNAs (NCRNAs).
After the mRNA is transcribed from the gene, it attaches to the ribosomes of the cell’s protein manufacturing plant. The ingredient supplier of the factory is TRNA.
The key function of RNA exosomes is to produce mature RRNA needed to construct functional ribosomes. RNA exosomes also degrade mRNA labeled for removal.
Unique signature
this RNA The paper studies how different disease-causing mutations in RNA exosomes have different cellular effects. To simulate these diseases, the researchers introduced mutations associated with human diseases into the corresponding four genes in yeast.
The researchers found that these mutations specifically affected NCRNA, the mRNA and ribosomal protein genes involved in metabolism. They were also able to identify defects used in the process unit to make ribosomes.
Importantly, this study shows that different extraRNA fibroid mutations have unique molecular characteristics that affect RNA monitoring, ribosome production, and protein synthesis. This uniqueness explains the different clinical outcomes in different patients with RNA exosome mutations and emphasizes the value of functional modeling to understand the disease.
Human Model
exist G3 The paper, researchers report creating a “humanized yeast model” by replacing specific yeast RNA exosomes with their human or mouse counterparts. Of the nine core components, six can be replaced in this way. Of these six, three still allow the yeast to grow almost normally.
They then mutated these genes in their model, which are known to cause brain diseases in humans. This model helped them identify precise genetic variants that cause functional defects, including previously known mutations and new mutations.
In each case, the team was also able to demonstrate that the mutation directly destroyed the RNA exosomes, rather than some mediating process.
The study determined that the humanized yeast model is a convenient platform for testing human RNA exosomes that are poorly mutations rather than those.
All in all, studies have shown that disease mutations that damage human RNA exosomes are also in yeast. In the future, drugs that mitigate damage in yeast may also prove useful in humans.
DP Kasbekar is a retired scientist.
publishing – May 11, 2025 at 06:00 AM IST
