Circular RNAs: diversity of form and function

Circular RNAs: diversity of form and function

2014 | ERIKA LASDA and ROY PARKER
Circular RNAs (circRNAs) are a diverse class of RNA molecules that can be formed through various mechanisms, including direct ligation of 5' and 3' ends of linear RNAs, RNA processing intermediates, and backsplicing events. They possess unique properties such as resistance to exonucleases, the ability to rearrange genomic information, and constraints on RNA folding. CircRNAs have been shown to function as templates for viroid and viral replication, as intermediates in RNA processing, as regulators of transcription, as snoRNAs, and as miRNA sponges. CircRNAs are found in a variety of biological contexts, including viroids, hepatitis delta virus, and introns. They can be produced through the splicing of pre-mRNA, where a downstream 5' splice site is joined to an upstream 3' splice site, resulting in a circular RNA. This process, known as backsplicing, leads to the formation of circRNAs that can be detected through RNA sequencing and other methods. CircRNAs are often stable and can be enriched using techniques such as RNase R resistance. CircRNAs have been implicated in various biological functions, including the modulation of miRNA activity. For example, the circRNA ciRS-7/CDR1as functions as a miRNA sponge, sequestering miR-7 and potentially modulating its activity. Other circRNAs, such as Sry, have been shown to function as miRNA sponges as well. Additionally, circRNAs may play a role in regulating alternative splicing by influencing the splicing pattern of pre-mRNA. The biogenesis, localization, and degradation of circRNAs are areas of active research. CircRNAs are typically transported to the cytosol and are not associated with ribosomes, suggesting they are not generally translated. They are also resistant to degradation, which may contribute to their stability. CircRNAs have been implicated in disease, with some circRNAs showing altered expression in disease states such as Alzheimer's disease and prion disease. Despite the growing understanding of circRNAs, many questions remain about their biological roles, regulation, and functions. Research continues to explore the potential of circRNAs in both disease and therapeutic applications, with the possibility of using engineered circRNAs as molecular tools or therapeutic agents.Circular RNAs (circRNAs) are a diverse class of RNA molecules that can be formed through various mechanisms, including direct ligation of 5' and 3' ends of linear RNAs, RNA processing intermediates, and backsplicing events. They possess unique properties such as resistance to exonucleases, the ability to rearrange genomic information, and constraints on RNA folding. CircRNAs have been shown to function as templates for viroid and viral replication, as intermediates in RNA processing, as regulators of transcription, as snoRNAs, and as miRNA sponges. CircRNAs are found in a variety of biological contexts, including viroids, hepatitis delta virus, and introns. They can be produced through the splicing of pre-mRNA, where a downstream 5' splice site is joined to an upstream 3' splice site, resulting in a circular RNA. This process, known as backsplicing, leads to the formation of circRNAs that can be detected through RNA sequencing and other methods. CircRNAs are often stable and can be enriched using techniques such as RNase R resistance. CircRNAs have been implicated in various biological functions, including the modulation of miRNA activity. For example, the circRNA ciRS-7/CDR1as functions as a miRNA sponge, sequestering miR-7 and potentially modulating its activity. Other circRNAs, such as Sry, have been shown to function as miRNA sponges as well. Additionally, circRNAs may play a role in regulating alternative splicing by influencing the splicing pattern of pre-mRNA. The biogenesis, localization, and degradation of circRNAs are areas of active research. CircRNAs are typically transported to the cytosol and are not associated with ribosomes, suggesting they are not generally translated. They are also resistant to degradation, which may contribute to their stability. CircRNAs have been implicated in disease, with some circRNAs showing altered expression in disease states such as Alzheimer's disease and prion disease. Despite the growing understanding of circRNAs, many questions remain about their biological roles, regulation, and functions. Research continues to explore the potential of circRNAs in both disease and therapeutic applications, with the possibility of using engineered circRNAs as molecular tools or therapeutic agents.
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