A study jointly led by researchers from Bar-Ilan University and the Weizmann Institute of Science found that a certain snoRNA affects both a chemical change in ribosomal RNA and ribosome folding, thereby altering the parasite's translation patterns.
The parasiteLeishmania Lives in two very different worlds. Part of its life cycle takes place in the sand fly, and another part inside mammalian cells. With each such transition, the temperature, nutrient availability, and immune environment change, so the parasite must quickly adapt its protein production systems.
New research, jointly led by Prof. Shulamit Michaeli מBar-Ilan University, Prof. Ada Yonath from the Weizmann Institute of Science and their colleagues, points to an additional layer of control: a molecule RNA Small type snoRNA is not limited to directing a chemical change in ribosomal RNA, but also affects the physical structure of theribosome and the types of mRNA translated in it.
The ribosome is not a fixed machine.
The ribosome is sometimes described as the cell's protein factory: it reads the instructions from mRNA and assembles amino acids into protein. However, in recent years, evidence has been accumulating that ribosomes are not necessarily exactly the same in every situation, and that chemical and structural changes can affect how they work.
The researchers mapped more than 100 sites where the ribosomal RNA of three Leishmania species undergoes a chemical modification called 2'-O-methylation. One site, called Am479, stood out: the level of modification was higher at the stage when the parasite was adapted to life inside a mammal.
The change is directed by a snoRNA molecule called LM/LD32Cs1C1. Normally, molecules of this type serve as a kind of "guide" for enzymes that carry out chemical changes in RNA. Here, it turned out that the molecule has an additional role.
Both chemical modification and folding assistance
When the researchers modified the snoRNA, they found that it affected a region of the ribosome called H68, which is distant from the Am479 site. The result suggests a chaperone-like role: the molecule helps ribosomal RNA reach a specific structure, in addition to its role in directing methylation.
A sharp reduction in snoRNA levels impaired the growth rate of theParasites And in general protein translation. The researchers also did not identify molecules in active ribosomes that completely lack the Am479 change, a finding that supports its importance for the proper functioning of the translation system.
However, it should not be concluded that this single change is a "switch" that turns the parasite on or off. The ribosome is a complex system, and there are additional backup and control mechanisms in the cell.
More than a thousand transcripts were affected
When the researchers increased snoRNA expression, the translation patterns of more than a thousand mRNA molecules changed. The changes were also linked to the composition of the tRNA found with the ribosomes and the use of different codons.
This means that the parasite may change not only which genes it transcribes, but also the characteristics of the machinery that translates the transcripts into proteins. This provides another way for the sandfly to rapidly adapt to the environment inside a mammal.
"Specialized" ribosomes as a biological principle
The research fits into a growing field of dynamic or specialized ribosomes. According to this concept, the cell can to some extent alter the composition of the ribosome, the chemical changes to its RNA, and its local structure, thereby influencing which proteins are produced and with what efficiency.
In Leishmania, this possibility is particularly interesting because the parasite must move between very different hosts. It also raises a broader question: to what extent similar mechanisms exist in other organisms, including human cells.
The research does not yet present a treatment for Leishmania. Before the mechanism can be turned into a drug target, it will need to be shown that it can be selectively targeted in the parasite, without damaging the host's ribosomes and RNA systems.
Questions and Answers
What is snoRNA?
snoRNA is a small RNA found primarily in the nucleus and aids in the processing and maturation of ribosomal RNA. Some snoRNA molecules direct enzymes to specific sites where chemical changes occur.
What's new in the research?
The researchers found that a particular snoRNA molecule in Leishmania plays a dual role: it directs a chemical change in ribosomal RNA and also affects its folding and ribosome structure.
Does the finding already suggest a cure for leishmania?
No. This is basic research that identifies an important mechanism in the functioning of the parasite. Drug development will require proof that the mechanism can be disrupted safely and selectively.
Why is the ribosome important for parasite adaptation?
The ribosome determines how RNA transcripts are translated into proteins. Altering its properties can rapidly alter the set of proteins a cell produces when its environment changes.
The scientific article
More on the subject on the science website
- Not just a Nobel Prize: The long road Ada Yonath took to turning the ribosome into the key to understanding antibiotics
- The Ribosome: The Key to Life at the Atomic Level – Part II
- The Ribosome: The Key to Life at the Atomic Level – Part 3
- Sandfly and Leishmania bites
For the scientific article: Opening the scientific article
