Research shows how ‘junk’ RNA controls our genes

Researchers at Arizona State University have made a significant advance in understanding how genes are controlled in living organisms. The new study, published in the journal Nucleic Acid Researchfocuses on critical fragments of RNA in the tiny, 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 genes in DNA are turned on and off after they are transcribed into RNA. With this data, scientists can make better predictions about how small RNA molecules (miRNAs) interact with genes to control their activity. The researchers also explored crucial regions of the 3’UTRs that help process and regulate RNA molecules.

By studying the genetic material of 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 20 years of hard work. We finally have a complete picture of how genes are formed in higher organisms,” says Marco Mangone, corresponding author of the new study.

“With this comprehensive dataset, we can now identify and study all the regulatory and processing elements within these gene sections. These elements determine the duration of gene expression, their specific location 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 the School of Life Sciences at ASU.

Genes are only half the story

Genes are segments of DNA that contain the blueprints for an astonishing diversity of life on Earth. But part of the secret to this versatility lies not in the genes themselves, but in how their effects are finely tuned. Genes provide the instructions for making proteins, which play a critical role in building and repairing cells and tissues, speeding up chemical reactions, and defending the body against pathogens.

To make proteins, genes need an intermediary molecule called RNA. In 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 gives the body enormous flexibility by regulating how genes are expressed.

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

3’UTRs are segments of RNA located at the end of a messenger RNA molecule. They help regulate how and when proteins are produced by controlling the stability and efficiency of the mRNA. This regulation enables dynamic responses to environmental changes and helps control protein production, which is essential for adapting to diverse physiological needs.

The 3’UTR reconsidered

Initially, non-coding RNAs such as 3’UTRs were considered non-essential genetic fragments because they did not themselves encode proteins. However, recent research reveals that they are essential for modifying gene behavior and influencing the stability, localization, and efficiency of mRNA translation. Translation refers to the process of converting RNA into proteins composed of amino acid sequences.

3’UTRs are an integral part of a sophisticated and highly adaptable system of control and balance of 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 have known little about these genes until now. The new study fills that gap by mapping the 3’UTRs of nearly every gene in C. elegans, providing the most comprehensive map of its kind for an animal.

A window into gene function and disease

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

The organism shares many essential biological pathways with humans, making it valuable 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 precise gene manipulation.

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 common in C. elegans than previously thought. This challenges previous beliefs and highlights the complexity of gene regulation. Using this new data, the scientists updated their predictions about how microRNAs interact with genes.

The results of this new study have far-reaching implications for human health. Problems with genetic 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 a critical resource for scientists studying genetics and human health. The ASU team plans to continue their research to explore in more detail how these regulatory elements work and how they play a critical role in gene control.