Genome-wide profiling and functional characterization of circular RNAs in neural development and injury: insights from a rat model research

Circular RNAs (circRNAs) have re-emerged as promising gene regulators in various physiological and pathological conditions. However, the expression patterns of circRNAs in the developing spinal cord of mammals and the comprehensive distribution of circRNAs across different tissues remain poorly understood. In this study, rats were used as the model organism. We conducted a comprehensive analysis of 15 RNA-Seq datasets comprising 217 rat samples and developed a web-based resource, CiRNat, to facilitate access to these data. We identified 15,251 credible circRNAs and validated them through experimental approaches. Notably, we observed two significant time points for circRNA increase during spinal cord development, approximately at embryonic day 14 (E14d) and postnatal week 4 (P4w). Analysis of circRNA expression in various rat tissues revealed higher expression levels in central nervous system tissues compared to peripheral nervous system tissues and other tissues. Furthermore, some highly abundant circRNAs exhibited tissue- and species-specific expression patterns and differed from their cognate linear RNAs, such as those derived from Gigyf2. Integrating polysome profiling and bioinformatic predictions suggested potential functions of certain circRNAs as miRNA sponges and translational templates. Collectively, this study provides the first comprehensive landscape of circRNAs in the developing spinal cord, offering an important resource and new insights for future exploration of functional circRNAs in central nervous system development and related diseases.