Inverted Alu repeats: friends or foes in the human transcriptome

Inverted Alu repeats: friends or foes in the human transcriptome

2024 | Keonyong Lee, Jayoung Ku, Doyeong Ku, and Yoosik Kim
Inverted Alu repeats (IRAlus) are double-stranded RNAs formed by Alu elements with opposite orientations, which are abundant in the human genome. These IRAlus play key roles in immune responses and gene regulation. They are recognized by dsRNA sensors like MDA5 and PKR, leading to antiviral signaling and innate immune activation. IRAlus can also regulate gene expression through post-transcriptional mechanisms, such as influencing circular RNA (circRNA) biogenesis, alternative splicing, and mRNA stability. IRAlus are involved in the formation of dsRNAs that can activate immune pathways, and their dysregulation is linked to immune-related disorders. RNA editing and interactions with RNA-binding proteins (RBPs) modulate IRAlus activity, and misregulation can contribute to diseases. ADAR1-mediated A-to-I editing can alter IRAlus structure and function, affecting their immunogenicity and gene regulatory roles. IRAlus are also involved in the regulation of 3' UTRs, influencing mRNA localization and stability. Future research aims to explore the regulatory mechanisms of IRAlus, their potential as therapeutic targets, and their role in disease pathogenesis. Synthetic IRAlus may offer new strategies for cancer immunotherapy by modulating innate immune responses. Overall, IRAlus are essential regulators of gene expression and immune responses in human cells.Inverted Alu repeats (IRAlus) are double-stranded RNAs formed by Alu elements with opposite orientations, which are abundant in the human genome. These IRAlus play key roles in immune responses and gene regulation. They are recognized by dsRNA sensors like MDA5 and PKR, leading to antiviral signaling and innate immune activation. IRAlus can also regulate gene expression through post-transcriptional mechanisms, such as influencing circular RNA (circRNA) biogenesis, alternative splicing, and mRNA stability. IRAlus are involved in the formation of dsRNAs that can activate immune pathways, and their dysregulation is linked to immune-related disorders. RNA editing and interactions with RNA-binding proteins (RBPs) modulate IRAlus activity, and misregulation can contribute to diseases. ADAR1-mediated A-to-I editing can alter IRAlus structure and function, affecting their immunogenicity and gene regulatory roles. IRAlus are also involved in the regulation of 3' UTRs, influencing mRNA localization and stability. Future research aims to explore the regulatory mechanisms of IRAlus, their potential as therapeutic targets, and their role in disease pathogenesis. Synthetic IRAlus may offer new strategies for cancer immunotherapy by modulating innate immune responses. Overall, IRAlus are essential regulators of gene expression and immune responses in human cells.
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