Researchers recognize the critical challenge for ribosome generation

UTSW researchers understand the critical challenge for ribosome generation

Human cells with new ribosomes (green), old ones (red), and a cover between the two (yellow). The label provides information on the dynamics of ribosome production, which can vary between different cells. Available: UT Southwestern Medical Center

UT Southwestern researchers have identified a four -protein complex that has been shown to play an important role in the formation of ribosomes – organelles that serve as a protein building block for cells – as well as a surprising component in neurodevelopmental diseases. The following information, published at Website Informationcan lead to new ways to regulate ribosome function, which can affect a variety of conditions related to human health.

“Ribosomes are important for life, but we have no complete understanding of how they assemble and how they regulate the ribosome process,” said Michael Buszczak, Ph.D. D., Professor of Molecular Biology and faculty. of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “Our findings shed much light on these questions.”

Dr. Buszczak explained that ribosomes are found in different sizes in every cell of every living thing on Earth. Because of their important role as protein producers, he added, different types of these natural structures can have deleterious effects. For example, cancer increases ribosome activity to increase protein production required for unchecked cell division. In addition, a group of rare diseases called ribosomopathies – characterized by normal ribosome function – are presented with a variety of symptoms including anemia, craniofacial defects, and deformity.

Although ribosomes have different types, most of what is known about ribosome biogenesis comes from the well -known model, yeast. The origins of this similar process are for human ribosome biogenesis, Drs. Buszczak said, but no details. Therefore, no details are known to model the human ribosome generation.

To learn more about this process, Dr. Buszczak, Chunyang Ni, a graduate student at the Buszczak Institute, and their colleagues, including Jun Wu, Ph.D., Assistant Professor of Molecular Biology at UTSW, began the development. Developing a technology that causes old ribosomes to turn red and new ribosomes. the green will shine. The researchers used this tool on a variety of human cell phones, verifying different numbers of ribosome activity in each.

Using a gene regulator called CRISPR, the researchers analyzed the types of genes to identify important players in ribosome biogenesis. Their search revealed four genes called CINP, SPATA5L1, C1orf109, and SPATA5. Further research has shown that the combination of these genes makes it difficult to remove a placeholder protein from the ribosomes when the combination is almost complete, allowing another protein to take its place. ribosome maturation.

Previously, the action of SPATA5 in cells was not observed; however, this change has been associated with neurodevelopmental diseases such as microcephaly, hearing loss, epilepsy, and disability. When the researchers inserted two of these mutations into cells to create a mutant SPATA5 protein, the cells were unable to produce the normal level of active ribosomes – thought to be possible. in these neurodevelopmental disorders develop ribosome problems.

Dr. Buszczak said he and his colleagues plan to learn why the central nervous system is known to be more susceptible to ribosomal problems than other cell types. He added that this knowledge could lead to new treatments for cancer, ribosomyopathy, and other conditions affected by overwork or the production of proteins.

Other UTSW researchers who contributed to this research were Daniel A. Schmitz, Jeon Lee, and Krzysztof Pawłowski.

Dr. Buszczak is an EE and Greer Garson Fogelson Scholar in Medical Sciences. Dr. Wu is a Virginia Murchison Linthicum Scholar in Medical Research and a Scholar Prevention and Research Institute of Texas (CPRIT).

Researchers use bacterial protein to detect and rescue ‘stalled’ ribosomes.

More information:
Chunyang Ni et al, The characterization of heterochronic ribosomes revealing that C1ORF109 and SPATA5 control a posterior function in the human ribosome group, Website Information (2022). DOI: 10.1016 / j.celrep.2022.110597

Presented by UT Southwestern Medical Center

Directions: Researchers identify critical complexity for ribosome generation (2022, March 29) Retrieved 29 March 2022 from

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