Research shows how RNA ‘junk’ controls our genes

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 crucial pieces 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 who study 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 of this model organism, researchers are gaining deeper insight into the mysteries of gene behavior, leading to greater understanding of fundamental biological processes essential to human health and disease.

“This monumental work is a 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 complete dataset, we can now localize and study all regulatory and processing elements within these gene sections. These elements determine the duration of gene expression, their specific locations within cells, and the required expression level.”

Mangone is a researcher in 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 segments of DNA that contain the blueprints for an astonishing diversity of life on Earth. Part of the secret to this versatility, however, lies not in the genes themselves but in the way their effects are delicately tuned. Genes provide the instructions for making proteins, which play essential roles in building and repairing cells and tissues, speeding up chemical reactions, and defending the body against pathogens.

To produce proteins, genes require an intermediary 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. While our DNA genome is fixed from birth, RNA gives the body tremendous flexibility by regulating how genes are expressed.

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

3’UTRs are sections of RNA that are 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 allows for dynamic responses to changes in the environment and enables control over protein production, which is essential for adapting to different physiological needs.

3’UTRs reconsidered

Initially, noncoding 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 modifying gene behavior and influencing mRNA stability, localization, and translation efficiency. 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. 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 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 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. 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 unraveling 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 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 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 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 explore how these regulatory elements work and their crucial influence on gene control.