Loss of circRNAs from the crh‐1 gene extends the mean lifespan in Caenorhabditis elegans

Abstract

CircRNAs are a recently appreciated class of RNAs generated by backsplicing (Li et al., 2018). Most characterized circRNAs are produced from exons of protein-coding genes (Zhang et al., 2014).CircRNAs lack free ends, resulting in greater resistance to exoribonuclease digestion compared to their linear RNA counterparts (Jeck et al., 2013). Interestingly, circRNAs were found to accumulate in the brains of Drosophila and rodents during aging (Gruner et al., 2016;

Loss of age-accumulatedcrh-1circRNAs ameliorate amyloid β-induced toxicity in aC. elegansmodel for Alzheimer’s disease

“…We favor the possibility that circ-crh-1 interacts with RNA-binding proteins (RBPs) to regulate their expression and function by acting as a sponge, decoy, scaffold or recruiter, which could affect the fate of mRNA targets of RBPs through post-transcriptional processes (Chen, 2020;Patop et al, 2019). In this scenario, and consistent with loss of circ-crh-1 expression resulting in transcriptomic changes (Knupp et al, 2022), circ-crh-1 may sequester away RBPs from col-49 mRNA targets, which in turn alters its expression.…”

“…CircRNAs accumulate during the normal process of aging in C. elegans (Cortés-López et al, 2018) , Drosophila (Hall et al, 2017; Westholm et al, 2014), and mice (Gruner et al, 2016) and are found to play both positive and negative roles in the aging of C. elegans , Drosophila , and various mammalian tissues (Kim et al, 2021; Knupp and Miura, 2018). Prominent examples include the extension of lifespan through circSfl transgenic overexpression in Drosophila (Weigelt et al, 2020) and the loss of the circRNA derived from the host gene crh-1 /CREB in C. elegans (Knupp et al, 2022).…”

“…Previously, we demonstrated that a majority of circRNAs expressed in C. elegans accumulate during aging (Cortés-López et al, 2018). Using CRISPR/Cas9, we genetically removed two abundant age-accumulated circRNAs derived from the crh-1 gene (circ- crh-1 ) encoding the homolog of CREB without disrupting the linear RNA and its associated activated protein (Knupp et al, 2022). Genetic loss of this age-accumulated circ- crh-1 extended the mean lifespan of C. elegans (Knupp et al, 2022), suggesting that circ- crh-1 abundance might contribute to age-related decline.…”

“…Using CRISPR/Cas9, we genetically removed two abundant age-accumulated circRNAs derived from the crh-1 gene (circ- crh-1 ) encoding the homolog of CREB without disrupting the linear RNA and its associated activated protein (Knupp et al, 2022). Genetic loss of this age-accumulated circ- crh-1 extended the mean lifespan of C. elegans (Knupp et al, 2022), suggesting that circ- crh-1 abundance might contribute to age-related decline. Here, we extended our findings by testing the impact of circ- crh-1 removal on a severe model of inducible amyloidosis in C. elegans .…”

Circular RNAs in the Origin of Developmental Lung Disease: Promising Diagnostic and Therapeutic Biomarkers

“…In fact, it was found that it is not exon sequences but circRNA’s complementary introns that regulate circRNA synthesis [ 28 , 36 ]. Moreover, complementary side sequences are enriched with circRNA introns in various species such as Caenorhabditis elegans, rodent, pig, and human [ 37 , 38 , 39 , 40 ].…”