Real-Time Ribosome Assembly
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Ribosome Assembly Rna Discovery – How RNA Molecule Folds Revealed

A research team from the Stanford University and Scripps Research Institute recorded in real-time an essential phase in the ribosome assembly ( Ribosome assembly is a complex process and is the evolutionarily ancient “molecular machines” that makes all the essential proteins in cells for all life forms.

This achievement is reported in the journal Cell. The study reveals detailed information that was never known before about how strands of ribonucleic acid (RNA), which are the cellular molecules that are inherently sticky and prone to misfold, are “chaperoned” by ribosomal proteins into folding precisely and forms one of the main components of ribosomes.

Earlier it was believed that the ribosomes are assembled in a strictly controlled and step-wise process. The findings in this study reversed the longstanding belief of ribosome assembly.

Dr. James R. Williamson, a professor in the Department of Integrative Structural & Computational Biology at Scripps Research, says, “We revealed a far more chaotic process than what was seen in the earlier dominant theory in the field. The process seems more like a trading pit on Wall Street and is not a sleek Detroit assembly line.”

Williamson’s lab and

the lab of Joseph Puglisi, Ph.D., a professor at Stanford University, collaborated for this study. The work is of significant importance in the field of basic cell biology. Along with this, it should also be useful for bringing significant advancements in medicines. For example, inhibiting bacterial ribosomes is how some of the current antibiotics work; this new study gives way to the possibilities of creating antibiotics in the future, which can target the bacterial ribosomes with higher specificity and with lesser side effects.

Most importantly, this study gives biologists a novel approach for studying thousands of RNA molecules that are always active in a typical cell.

The first author, Dr. Olivier Duss, a postdoctoral research fellow in the Department of Integrative Structural & Computational Biology at Scripps Research, says, ” The process of how RNA fold when there are produced while proteins are assembled on them in the ribosome assembly, can be now examined in detailed. This process has been a tough study because of involving many distinct biological processes that are dependent on each other, and they had to be identified together.”

The research team made use of “zero-mode waveguide single-molecule fluorescence microscopy,” which is an advanced imaging technology. This technology has been used by them in recent years for tracking the RNAs and proteins in real-time. Both RNA and proteins make up the ribosomes, which show a molecular partnership that is commonly believed to go back almost to the dawn of life in the world.

Last year, a proof-of-principle research study was published, where the scientists recorded an early, brief, and relatively well-studied stage of ribosome assembly from the bacterium E. coli. It was by using the transcription or copying its corresponding gene of a ribosomal RNA and the initial interactions of a ribosomal protein with this strand of RNA.

This approach was extended to this new research study. Here in this study, not just the transcription of a ribosomal RNA was tracked, but also it could follow the real-time folding.

The research team extended this approach in this new study. The transcription of ribosomal RNA was tracked along with the tracking of its real-time folding process. This allowed having an in-depth look at the complex and unknown part of the ribosome assembly of E. coli. With assistance from eight protein partners, a formation of a major component or an entire domain of the E. coli ribosome gave rise to the structure.

The significant finding in this study was that before the RNAs nestle into their final positions in the folded RNA-protein molecule, the folding of the RNA strands was guided by the ribosomal protein partners through many temporary interactions with the RNA strand. This discovery leads to the possibility of the presence of unidentified RNA assembly aspects, mostly proteins, that could improve the RNA folding efficiency, and which were absent in their lab-dish-type imaging experiments but are found in the cells.

“Our research study shows that in ribosomal RNA-folding, and perhaps more usually in RNA-folding in cells, numerous proteins help fold RNA though weak, transient and semi-specific interactions with it,” Duss says.

This study now allows the researchers to study further not just the remaining ribosome assembly involving various strands of RNA and dozens of proteins. Still, it also lets them examine many different types of RNA-folding and RNA-protein interactions in cells.

On the whole, this study can help in identifying RNA misfolds and can give insights on how to correct such misfolding. The improper folding of RNA could have links with many diseases or involve the processing of RNAs in the cells.

Improvements can be made on the treatments which already target the ribosomes. Some of the present antibiotics, like a class of antibiotics, called aminoglycosides work by binding to the bacterial ribosome sites that are not present on human ribosomes. There can be side effects from such drugs because they can cause damage to the ribosomes of good bacteria, like the ones in the gut.

Duss says, “By completely understanding how ribosome assembly is formed and its function in bacteria, we can spare the good bacteria and potentially target a narrower group of harmful bacterial species, avoiding the side effects in patients. Since the ribosome’s functions also include protein markers, they are important to the survival of fast-growing tumor cells. There are already many classes of cancer drugs that work by slowing down the formation of the ribosome. Understanding the human ribosome in a much better way would ultimately enable the ribosome assembly to be targeted more precisely and could potentially block cancer growth.”

SOURCE

Editors Note- The Ribosomal Assembly RNA Discovery, Ribosome Assembly and RNA Discovery. How RNA Molecules folds. Ribosome Assembly RNA Discovery by Stanford University and Scripps Research Institute scientists.

Author: Prathibha HC

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