Journal
GENOME BIOLOGY
Volume 16, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13059-015-0690-5
Keywords
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Funding
- NCI [R00 CA168987-03]
- Baxter Family Fellowship
- NLM training grant [2T15LM007033-29]
- UCSD Department of Reproductive Medicine
- NIH [P01 HL094374, R01 HL084642, P01 GM081719, U01 HL100405]
- NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director
- California Institute for Regenerative Medicine Bridges to Stem Cell Research Award
- [U01HL126494]
- NCI NIH HHS [R00 CA168987-03, R00 CA168987] Funding Source: Medline
- NHLBI NIH HHS [U01HL126494, U01 HL126494, U01 HL100405, R01 HL084642, P01 HL094374] Funding Source: Medline
- NIGMS NIH HHS [P01 GM081719] Funding Source: Medline
- NLM NIH HHS [T15 LM007033] Funding Source: Medline
- NLM NIH HHS [2T15LM007033-29, T15 LM007033] Funding Source: Medline
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Background: The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biological contexts where circular RNAs are regulated will shed light on potential functional roles they may play. Results: We present a new algorithm that increases the sensitivity and specificity of circular RNA detection by discovering and quantifying circular and linear RNA splicing events at both annotated and un-annotated exon boundaries, including intergenic regions of the genome, with high statistical confidence. Unlike approaches that rely on read count and exon homology to determine confidence in prediction of circular RNA expression, our algorithm uses a statistical approach. Using our algorithm, we unveiled striking induction of general and tissue-specific circular RNAs, including in the heart and lung, during human fetal development. We discover regions of the human fetal brain, such as the frontal cortex, with marked enrichment for genes where circular RNA isoforms are dominant. Conclusions: The vast majority of circular RNA production occurs at major spliceosome splice sites; however, we find the first examples of developmentally induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, these results suggest a potentially significant role for circular RNA in human development.
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