Research shows how ‘junk RNA’ controls our genes

Arizona State University scientists have made significant progress in understanding how genes are controlled in living organisms. A new study published in the journal Nucleic acid researchfocuses on critical RNA fragments 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 DNA genes turn on and off after they are transcribed into RNA. Using this data, scientists can better predict how small RNA molecules (miRNAs) interact with genes to control their activity. The researchers also examined key regions of the 3’UTR that aid in the processing and regulation of RNA molecules.

By studying the genetic material in this model organism, scientists gain deeper insight into the secrets of gene behavior and shed 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 made in higher organisms,” says Marco Mangone, corresponding author of the new study.

“With this complete data set, we can now pinpoint 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 desired 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 the amazing 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 fine-tuned. Genes provide instructions for making proteins that play a vital role in building and repairing cells and tissues, speeding up chemical reactions, and protecting the body from pathogens.

Genes need an intermediary molecule called RNA to produce proteins. 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 into messenger RNA (mRNA), specialized segments of mRNA – the 3’UTR – can regulate how proteins are produced.

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

3’UTR revisited

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 key to modifying gene behavior and influencing mRNA stability, localization and 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 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 fundamental 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 precise manipulation of genes.

These properties make C. elegans a powerful tool for uncovering fundamental biological mechanisms 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 views and highlights the complexity of gene regulation. Using the new data, the researchers updated predictions of how microRNAs interact with genes.

The findings 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 created 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 influence on gene control.