Researchers at Arizona State University have made significant progress in understanding how genes are controlled in living organisms. The new study, published in the journal Nucleic acid researchtargets critical fragments of RNA in the small, transparent roundworm Caenorhabditis elegans (C. elegans).
The study provides a detailed map of the 3’UTR regions of RNA in C. elegans. 3’UTRs (untranslated regions) are RNA segments involved in gene regulation.
The new map is a valuable tool for scientists studying how DNA genes are turned on and off after they are transcribed into RNA. Using this data, scientists can make better predictions about how small RNA molecules (miRNAs) interact with genes to control their activity. The researchers also examined crucial regions of the 3’UTRs that help process and regulate RNA molecules.
By studying the genetic material in this model organism, researchers are gaining deeper insights into the mysteries of gene behavior, shedding light on fundamental biological processes essential to human health and disease.
“This monumental work represents the culmination of twenty years of hard work. We finally have a complete picture of how genes are formed in higher organisms,” said Marco Mangone, corresponding author of the new study. “With this complete data set, we can now locate and study all regulatory and processing elements within these gene sections. These elements determine the duration of gene expression, their specific locations in cells, and the level of expression required.”
Mangone is a researcher at the Biodesign Virginia G. Piper Center for Personalized Diagnostics and a professor in ASU’s School of Life Sciences.
Genes are only half the story
Genes are stretches of DNA that contain the blueprints for an astonishing diversity of life on Earth. Part of the secret of this versatility, however, lies not in the genes themselves, but in the way their effects are subtly tuned. Genes provide the instructions for making proteins, which play an essential role in building and repairing cells and tissues, speeding up chemical reactions and defending the body against pathogens.
To produce proteins, genes need an intermediate molecule called RNA. During this process, DNA is first copied into RNA, which acts as a bridge between the DNA template and the resulting proteins. Although our DNA genome is fixed from birth, RNA provides the body with enormous flexibility by regulating how genes are expressed.
Once genetic instructions are transcribed from DNA to messenger RNA (mRNA), specialized segments of the mRNA (the 3’UTRs) can control how the proteins are produced.
3’UTRs are pieces of RNA located at the end of a messenger RNA molecule. They help control how and when proteins are made by controlling the stability and efficiency of the mRNA. This regulation enables dynamic responses to environmental changes and enables control over protein production, which is essential for adaptation to different physiological needs.
3’UTRs reconsidered
Initially, non-coding RNAs such as 3’UTRs were considered non-essential genetic fragments because they do not code for proteins themselves. However, recent research shows that they are crucial for altering the behavior of genes and influencing the stability, localization and translation efficiency of mRNA. Translation refers to the process of converting RNA into proteins composed of sequences of amino acids.
3’UTRs are an integral part of a sophisticated and highly adaptable system of checks and balances on protein production. Furthermore, these RNA regulatory elements often contain binding sites for other elements responsible for protein regulation, including microRNAs and RNA-binding proteins.
Despite their importance, scientists previously knew little about them. The new study addresses this gap by mapping 3’UTRs for nearly all genes in C. elegans, creating the most complete map of its kind for each animal.
A window into gene function and disease
C. elegans is a small, transparent nematode that is one of the most extensively studied model organisms in biological research. Its significance lies in its simplicity, short life cycle and well-mapped genetic structure.
The organism shares many essential biological pathways with humans, making it invaluable for studying gene function, development and disease processes. The transparent body allows researchers to observe cellular processes in real time, and the genetic makeup allows the precise manipulation of genes.
These features make C. elegans a powerful tool for uncovering fundamental biological mechanisms that are often conserved among species, including humans.
The study found that the process of switching between different 3’UTRs is less common in C. elegans than previously thought. This challenges previous beliefs and highlights the complexity of gene regulation. Using the new data, scientists have updated predictions about how microRNAs interact with genes.
The insights from the new study have far-reaching implications for human health. Problems with gene control can lead to diseases such as cancer, diabetes and neurological disorders. By providing a detailed map of 3’UTRs and their regulatory elements, the research offers new insights that could lead to better treatments and therapies.
The new dataset produced in the study will be an important resource for scientists studying genetics and human health. The ASU team plans to continue their research to further investigate how these regulatory elements work and their critical influence on gene control.
