RNA's Role in Life's Origins
Exploring RNA's dual function in genetics and catalysis.
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RNA is an essential molecule that plays two key roles: it carries genetic information and acts as a catalyst in biochemical reactions. This dual nature makes RNA an interesting candidate in discussions about the origin of life on Earth. Some scientists believe that in the earliest days of life, before DNA and proteins existed, RNA was the primary molecule for storing and using genetic information.
The Hypothetical RNA World
One idea, called the "RNA world" hypothesis, suggests that early life forms were based on RNA alone. In this scenario, RNA molecules were responsible for both storing genetic information and performing chemical reactions. Over time, DNA and proteins evolved, leading to the complex life forms we see today. Genetic remnants from this RNA world can still be found in the form of catalytic RNAS. Examples of such RNAs include ribosomal RNAs and Ribozymes, which are RNA molecules with catalytic abilities.
Modern RNA Fossils
Today, we can find simple RNA-based entities, like Viruses and viroids, that are considered living fossils. These entities give us insight into what early life might have looked like. Among the simplest of these ribozymes are a group that includes several well-studied members: hammerhead ribozymes, hairpin ribozymes, and others.
During the 1980s, researchers first identified small ribozymes in plant viruses and other organisms. In recent years, scientists have discovered that these ribozyme motifs are more widespread than initially thought, appearing in a variety of DNA genomes, including those of bacteria and even in human DNA.
The Hammerhead Ribozyme
The hammerhead ribozyme is particularly well-known. It is composed of three segments of double-stranded RNA that form a structure with a unique shape, allowing it to perform self-cleavage, a process where the RNA cuts itself. Depending on the structure of the ribozyme, there are different variations of the hammerhead ribozyme, known as type I, II, and III.
Each type has its own specific characteristics, and researchers have studied these to understand their functions better. The typical hammerhead ribozyme has a core of conserved nucleotides that are crucial for its activity.
Sequencing and the Growth of Microbial Diversity
Advancements in sequencing and computing technology have enabled scientists to uncover the diversity of microbial life forms. This research has highlighted not only the importance of proteins and ribosomal RNA but also the existence of diverse and contemporary RNA systems. Recent studies have revealed many new circular RNAs that contain self-cleaving ribozymes, expanding our understanding of RNA.
Viroid-like RNA Forms
The discovery of over 20,000 viroid-like entities, which include hybrids of RNA viruses and viroids, points to an intricate web of RNA-based life. This complexity challenges previous distinctions between different types of RNA entities and shows that we may have a modern RNA world filled with various mobile genetic elements.
Search for Small Self-Cleaving Ribozyme Variants
Research has recently focused on identifying small self-cleaving ribozymes in different families of fungal and plant RNA viruses. Surprisingly, these ribozymes do not seem to be involved in RNA processing during replication but may have adapted to play new roles in the life cycles of linear RNA viruses.
Findings in RNA Viruses
Using computer analyses, scientists screened known ribozyme families in viral sequences from public databases, leading to the identification of significant ribozyme motifs in various RNA viruses. For instance, in a family of multipartite viruses known as Chrysoviridae, about 42% of certain RNA segments contained a unique variant of the hammerhead ribozyme.
These motifs were located in specific regions of the viral genome, demonstrating how these ribozymes are retained across different segments of the virus.
Characteristics of Chrysovirus Ribozymes
The chrysoviral hammerhead ribozymes display distinct features. They can either have longer or shorter segments, affecting their ability to self-cleave efficiently. In laboratory experiments, researchers confirmed that certain variants with longer segments were capable of self-cleaving effectively, while shorter variants showed limited activity.
Other Types of RNA Viruses
Aside from chrysoviruses, other RNA viruses such as fusariviruses and megabirnaviruses also encode hammerhead ribozymes and other types, indicating that self-cleaving ribozymes are widespread among these viral families. Some viral genomes even have pairs of ribozymes close to each other, hinting at potential circular RNA formation.
Evidence of Self-Cleaving Activity in Vivo
Researchers sought to provide evidence for the self-cleaving activity of hammerhead ribozymes during viral infections. They focused on specific viruses infecting plants and fungi, using RNA collected from infected individuals. By analyzing their RNA, they found that molecules with both uncleaved and self-cleaved forms exist, confirming the activity of these ribozymes in a living system.
Translation Initiation
Role inBeyond their self-cleaving function, hammerhead ribozymes have been implicated in the process of translation initiation. The 5’ untranslated regions (UTRs) of certain RNA viruses contain ribozymes that may promote the initiation of protein synthesis. Experiments showed that mutations in these ribozymes disrupt their capacity to support translation, indicating that their structure and activity are crucial for this process.
Importance of Self-Cleaving Ribozyme Structure
The small size of hammerhead ribozymes, typically around 50-70 nucleotides, allows them to occupy significant portions of the viral RNA. While they perform self-cleavage, the way they interact with the cellular machinery involved in translation suggests they might serve dual functions.
Researchers propose that these ribozymes might aid in translation by providing the necessary structural elements to facilitate the recruitment of translation factors.
Evolutionary Significance
The discovery of these ribozymes sheds light on their possible evolutionary history, with many suggesting that they could have been among the first catalytic RNA molecules. However, most current knowledge about self-cleaving ribozymes stems from a small number of species, primarily found in viroid-like RNA forms.
As more studies reveal the presence of ribozymes across a broader range of organisms and environments, we begin to understand the potential roles these molecules play in various biological processes.
Conclusion
The study of RNA and its various forms offers significant insights into the foundations of life. The presence of self-cleaving ribozymes in both modern and ancient contexts emphasizes the importance of RNA in evolutionary biology, particularly regarding how early life forms may have functioned. The ongoing research in this area continues to uncover the complexity and versatility of RNA as a vital component of life on Earth.
In summary, RNA not only serves as a genetic messenger but also as a catalyst, bridging many essential processes in living organisms. As scientists continue to unravel the mysteries of RNA, we are likely to gain further insights into the origins of life and the evolution of biological systems.
Title: Self-cleaving ribozymes conserved in RNA viruses unveil a new role in protein translation
Abstract: Small self-cleaving ribozymes are catalytic RNAs originally discovered in viroid-like agents, which are infectious circular RNAs (circRNAs) postulated as relics of a prebiotic RNA world. In the last decade, however, small ribozymes have also been detected across the tree of life, from bacterial to human genomes, and more recently, in viral agents with circRNA genomes. Here we report the conserved occurrence of small ribozymes within the linear genomes of typical ds and ssRNA viruses from fungi and plants. In most 5-UTR regions of chrysovirids and fusarivirids, we find conserved type I hammerhead ribozymes (hhrbzs) showing efficient self-cleaving activity in vitro and in vivo. Similar hhrbzs, as well as hepatitis delta and twister ribozymes, were also detected in megabirna-, hypo-, fusagra- and toti-like viruses. These ribozymes occur as isolated motifs but also as close tandem pairs, suggesting that they are involved in the formation of [~]300 nt circRNAs. In vivo characterization of a chrysovirid hhrbz revealed its unexpected role in protein translation as an internal ribosome entry site (IRES). RNA structural comparison between the hammerhead three-way junction and the core domain of picornavirus IRES elements allow us to suggest that these simple ribozymes may follow a similar strategy to achieve cap-independent translation. We conclude that self-cleaving ribozymes, historically involved in the rolling circle replication of viroid-like agents, have been exapted towards translational functions in linear RNA viruses.
Authors: Marcos De la Peña, M. J. Lopez-Galiano, S. Chiba, M. Forgia, B. Navarro, A. Cervera, A. Babaian, F. Di Serio, M. Turina, M. De la Pena
Last Update: 2024-05-16 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.05.16.594327
Source PDF: https://www.biorxiv.org/content/10.1101/2024.05.16.594327.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
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