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An international research team has made significant progress in understanding the molecular mechanics of protein synthesis. Using advanced imaging technology, they visualized a critical step in how genetic information is translated into proteins. Their findings, published in Science, reveal how ribosomes, the molecular machines responsible for protein synthesis, interact with messenger RNA (mRNA) to initiate this essential process.
How Genes Communicate
Proteins are synthesized based on genetic instructions encoded in DNA. This requires a two-step process: transcription, where a DNA sequence is copied into mRNA, and translation, where ribosomes decode the mRNA to assemble amino acids into a protein. While much is known about translation, a major question has lingered—how do ribosomes locate the correct mRNA to begin translation?
To address the question, the research team used cryogenic electron microscopy (cryo-EM), reconstructing atomic-level models of bacterial ribosomes interacting with mRNA and associated molecules.
The Role of Key Molecular Interactions
The study focused on bacterial ribosomes, which can identify mRNA through multiple interactions: the Shine-Dalgarno sequence (an RNA motif), the RNA-binding protein S1, and the RNA polymerase enzyme. However, how these elements work together to guide mRNA to the ribosome was previously unclear.
The cryo-EM analysis revealed a detailed pathway on the ribosome's surface that facilitates the delivery of mRNA to the decoding site. This pathway enables precise interactions, minimizing the need for an extended search. “The surprising finding is that there really is a mechanism that has evolved to help mRNAs be delivered to the ribosome for translation,” said Michael Webster of the John Innes Centre, a senior author on the study.
Implications Beyond Bacteria
This newly elucidated mechanism answers a long-standing question in bacterial gene expression and has implications for plant biology. Chloroplasts, the photosynthetic organelles in plants, evolved from bacteria and appear to retain ribosomes that operate similarly.
“I was surprised how clearly our structural models show that the bacterial ribosome can make a path for the incoming mRNA. This molecular arrangement would clearly make the job of finding an mRNA to translate much easier,” Webster noted. His team plans to investigate how this mechanism contributes to producing photosynthetic proteins in chloroplasts, an area with potential relevance for developing climate-resilient crops.
This discovery deepens our understanding of a fundamental cellular process and opens new avenues for exploring how gene expression can be manipulated for scientific and agricultural advancements.
Citation:
Michael W. Webster et al., Molecular basis of mRNA delivery to the bacterial ribosome. Science 386, eado8476 (2024). DOI:10.1126/science.ado8476