Abstract
Circular (circ) RNAs have recently emerged as a novel class of transcripts whose identification and function remain elusive. Among many tissues and species, the mammalian brain is the organ in which circRNAs are more abundant and first evidence of their functional significance started to emerge. Yet, even within this well-studied organ, annotation of circRNAs remains fragmentary, their sequence is unknown, and their expression in specific cell types was never investigated. Overcoming these limitations, here we provide the first comprehensive identification of circRNAs and assessment of their expression patterns in proliferating neural stem cells, neurogenic progenitors, and newborn neurons of the developing mouse cortex. Extending the current knowledge about the diversity of this class of transcripts by the identification of nearly 4,000 new circRNAs, our study is the first to provide the full sequence information and expression patterns of circRNAs in cell types representing the lineage of neurogenic commitment. We further exploited our data by evaluating the coding potential, evolutionary conservation, and biogenesis of circRNAs that we found to arise from a specific subclass of linear mRNAs. Our study provides the arising field of circRNA biology with a powerful new resource to address the complexity and potential biological significance of this new class of transcripts.
Highlights
In the last few decades, the field of RNA biology has witnessed impressive developments
The reads were aligned to the reference mouse genome and unmapped reads used to identify the circularizing, backsplice junctions predictive of putative circRNAs (Fig S1B)
We provided the arising field of circRNA biology with the first resource describing their sequence and cell-specific expression during mammalian cortical development. This has allowed us to increase by threefold the number of circRNAs currently known, pointing out their full diversity and specificity in cell populations representing the lineage to neurogenic commitment
Summary
In the last few decades, the field of RNA biology has witnessed impressive developments. The lack of a 39 poly(A) tail and 59 capping provides this class of RNAs resistance to exonuclease activity and, an average longer half-live as compared with linear RNAs (Suzuki et al, 2006; Vincent & Deutscher, 2006; Jeck et al, 2013) Transcripts with these characteristics have long been known, but until recently, circRNAs were primarily found in viruses (Kos et al, 1986), and some reports indicated their origin from eukaryotic genomes (Nigro et al, 1991; Capel et al, 1993; Zaphiropoulos, 1996), these were still considered a rarity or a byproduct of splicing with no specific function. This view was completely changed very recently after the identification of thousands of circRNAs, including some with regulatory functions during brain development (Salzman et al, 2012; Hansen et al, 2013; Jeck et al, 2013; Memczak et al, 2013; Piwecka et al, 2017)
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