CircHTT(2,3,4,5,6) — co-evolving with the HTT CAG-repeat tract — modulates Huntington's disease phenotypes

Morandell, Jasmin; Monziani, Alan; Lazioli, Martina; Donzel, Deborah; Döring, Jessica; Oss Pegorar, Claudio; D’Anzi, Angela; Pellegrini, Miguel; Mattiello, Andrea; Bortolotti, Dalia; Bergonzoni, Guendalina; Tripathi, Takshashila; Mattis, Virginia B.; Kovalenko, Marina; Rosati, Jessica; Dieterich, Christoph; Dassi, Erik; Wheeler, Vanessa C.; Ellederová, Zdenka; Wilusz, Jeremy E.; Viero, Gabriella; Biagioli, Marta

doi:10.1016/j.omtn.2024.102234

Cited by 1 publication

(1 citation statement)

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“…CircRNAs typically arise from genes linked to synaptic functions. Although their physiological functions remain much less well studied compared to the linear version of the gene, circRNAs have been shown to play important roles in various aspects of brain development and functionality, including neural stemness and neurodegeneration during aging, cognition, and plasticity [6][7][8][9][10][11] . For instance, the loss of Cdr1as circRNA disrupts sensorimotor gating, a phenotype associated with several human neuropsychiatric disorders 12,13 .…”

Section: Introductionmentioning

confidence: 99%

ELAV mediates circular RNA biogenesis in neurons

Alfonso-Gonzalez,

Holec,

Gorey

et al. 2024

Preprint

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Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally (>75%) depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In brain tissue, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape.

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