Researchers from the Korea Advanced Institute of Science and Technology (KAIST) have made a discovery in the field of genetic regulation, highlighting the critical role of Alu elements in diseases such as tumor formation and neurodegenerative disorders.
Alu elements, which make up about 10 percent of the human genome, are known for their ability to regulate the efficiency of protein production from messenger RNA (mRNA).
The research, led by Professors Kim Yoo-sik of the Department of Chemical and Biomolecular Engineering and Lee Young-suk of the Department of Bio and Brain Engineering, identified that when mRNA features an Inverted Alu Repeat (IRAlu) structure formed by two Alu elements, it can impede mRNA's movement within the cell, leading to decreased protein production.
This new mechanism of disease onset, where specific mRNAs are regulated by IRAlus, resulting in suppressed gene expression and, consequently, disease, is an advancement in understanding genetic diseases.
Alu elements have traditionally been considered "selfish" sequences that replicate within the genome without contributing to protein information. However, this study showcases their potential in inhibiting protein translation by blocking the cytoplasmic movement of host mRNA.
Utilizing antibodies that can recognize IRAlu structures and next-generation sequencing, the researchers have compiled a list of mRNAs that are functionally inhibited by IRAlus, shedding light on a novel gene regulation mechanism that affects tumor suppressor genes and promotes tumor development through increased protein expression.
Furthermore, the team explored cancer treatment strategies using antisense oligonucleotides (ASOs), innovative RNA therapeutics that bind to complementary mRNA sequences to inhibit their function and restore protein expression.
A particularly intriguing aspect of the study is the identification of active gene regulation by IRAlus in neural cells, establishing a link between the excessive activity of this mechanism and neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig's disease.
"This study not only catalogs genes with Inverted Alu Repeat structures but also confirms for the first time their critical role in the onset of human diseases, particularly in tumor formation and neurodegenerative disorders,” Kim said. “Targeting IRAlus offers a fundamental and effective strategy for analyzing the mechanisms behind various degenerative diseases and developing treatments for tumors and aging-related conditions.”
The research results were published in Cell.