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Arizona State University researchers have made significant progress in understanding how genes are controlled in living organisms. The new study, published in the journal Nucleic acid researchfocused on critical RNA fragments 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 segments of RNA 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 improved predictions about how small RNA molecules (miRNAs) interact with genes to control their activity. The researchers also examined key regions of 3’UTRs that help process and regulate RNA molecules.

By studying the genetic material in this model organism, researchers gain deeper insight 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 20 years of hard work. We finally have the complete picture of how genes are formed in higher organisms,” says Marco Mangone, author of the new study.

“With this complete data set, we can now identify and study all the regulatory and processing elements in these gene sections. These elements determine the duration of gene expression, their specific locations in cells and the required level of expression.”

Mangone is a researcher in the Biodesign Virginia G. Piper Center for Personalized Diagnostics and a professor in the School of Life Sciences at ASU.

Genes are only half the story

Genes are segments of DNA that contain the blueprints for an amazing variety of life on Earth. However, part of the secret of this flexibility lies not in the genes themselves, but in how their effects are delicately fine-tuned. Genes provide the instructions for making proteins that play an essential role in building and repairing cells and tissues, speeding up chemical reactions, and defending the body against pathogens.

In order to make proteins, genes require 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.

After genetic instructions are transcribed from DNA into messenger RNA (mRNA), specialized segments of the mRNA – 3’UTRs – can regulate how proteins are made.

3’UTRs are regions of RNA located at the end of the messenger RNA molecule. They help manage how and when proteins are made by controlling the stability and efficiency of mRNA. This regulation enables dynamic responses to environmental changes and enables control of protein production, which is essential for adaptation to different physiological needs.

3’UTRs revisited

Initially, non-coding RNAs such as 3’UTRs were considered to be non-essential genetic fragments because they do not themselves code for proteins. However, recent research has revealed that they are critical for modifying gene behavior and influencing mRNA stability, localization, and translation efficiency. Translation refers to the process of converting RNA into proteins made up of sequences of amino acids.

3’UTRs are an integral part of a sophisticated and highly adaptive system of checks and balances on protein production. In addition, 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 the 3’UTRs for nearly all genes in C. elegans, providing the most complete map of its kind for any animal.

A window into gene function and disease

C. elegans is a small, transparent nematode that is one of the most widely studied model organisms in biological research. Its importance lies in its simplicity, short life cycle and well-mapped genetic structure.

The organism shares many basic biological pathways with humans, making it invaluable for studying gene function, development, and disease processes. Its transparent body allows researchers to observe cellular processes in real time, and its genetic makeup allows for the precise manipulation of genes.

These features make C. elegans a powerful tool for uncovering fundamental mechanisms of biology that are often conserved across species, including humans.

The study found that the process of switching between different 3’UTRs is less frequent in C. elegans than previously thought. This challenges earlier beliefs and highlights the complexity of gene regulation. Using the new data, the scientists updated predictions about how microRNAs interact with genes.

The insights gained 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 study offers new insights that could lead to better treatments and therapies.

The new data set obtained in the study will be a key resource for scientists studying genetics and human health. The ASU team plans to continue their research to further explore how these regulatory elements work and their critical impact on gene control.