Biogenesis of circular RNAs and their role in cellular and molecular phenotypes of neurological disorders.

Circular RNA (circRNA) is an unusual class of RNA-like structures composed by exonic and/or intronic sequences that are regulated by the backsplicing mechanism and by the spliceosome-mediated machinery. These circular transcripts tend to accumulate during aging in several human tissues, especially in the mammalian brain, and their expression is correlated with the occurrence of several human pathologies, including a broad spectrum of neurological disorders. Previous findings have also shown that circRNAs are significantly present in the neuronal tissue and are up-regulated during neurogenesis, with a significant number been derived from neural genes, suggesting these circular molecules are involved in the cellular and molecular phenotype of our brain. However, the complete biogenesis, the many types of circRNA molecules, and their involvement with neuronal phenotype and with the occurrence of pathologies are still a challenging avenue for researchers. In this updated review, we discuss the current findings of the biogenesis and the diversity of cirRNAs and their molecular involvement in neurological tissue phenotype. We also discuss how some circRNAs can act as sponge molecules, regulating the activity of microRNA expression over gene translation. Finally, we also show the correlation of altered circRNA expression in neurological disorders.

Modeling anorexia nervosa: transcriptional insights from human iPSC-derived neurons.

Anorexia nervosa (AN) is a complex and multifactorial disorder occurring predominantly in women. Despite having the highest mortality among psychiatric conditions, it still lacks robust and effective treatment. Disorders such as AN are most likely syndromes with multiple genetic contributions, however, genome-wide studies have been underpowered to reveal associations with this uncommon illness. Here, we generated induced pluripotent stem cells (iPSCs) from adolescent females with AN and unaffected controls. These iPSCs were differentiated into neural cultures and subjected to extensive transcriptome analysis. Within a small cohort of patients who presented for treatment, we identified a novel gene that appears to contribute to AN pathophysiology, TACR1 (tachykinin 1 receptor). The participation of tachykinins in a variety of biological processes and their interactions with other neurotransmitters suggest novel mechanisms for how a disrupted tachykinin system might contribute to AN symptoms. Although TACR1 has been associated with psychiatric conditions, especially anxiety disorders, we believe this report is its first association with AN. Moreover, our human iPSC approach is a proof-of-concept that AN can be modeled in vitro with a full human genetic complement, and represents a new tool for understanding the elusive molecular and cellular mechanisms underlying the disease.