Evolutionary Dynamics of Circular RNAs in Primates

Overview

Journal Elife

Specialty Biology

Date 2021 Sep 20

PMID 34542404

Citations 15

Authors

Gabriela Santos-Rodriguez

Irina Voineagu

Robert J Weatheritt

Affiliations

Soon will be listed here.

Abstract

Many primate genes produce circular RNAs (circRNAs). However, the extent of circRNA conservation between closely related species remains unclear. By comparing tissue-specific transcriptomes across over 70 million years of primate evolution, we identify that within 3 million years circRNA expression profiles diverged such that they are more related to species identity than organ type. However, our analysis also revealed a subset of circRNAs with conserved neural expression across tens of millions of years of evolution. By comparing to species-specific circRNAs, we identified that the downstream intron of the conserved circRNAs display a dramatic lengthening during evolution due to the insertion of novel retrotransposons. Our work provides comparative analyses of the mechanisms promoting circRNAs to generate increased transcriptomic complexity in primates.

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References

Baek D, Green P . Sequence conservation, relative isoform frequencies, and nonsense-mediated decay in evolutionarily conserved alternative splicing. Proc Natl Acad Sci U S A. 2005; 102(36):12813-8. PMC: 1192826. DOI: 10.1073/pnas.0506139102. View

Liang D, Wilusz J . Short intronic repeat sequences facilitate circular RNA production. Genes Dev. 2014; 28(20):2233-47. PMC: 4201285. DOI: 10.1101/gad.251926.114. View

Zhang X, Gingeras T, Weng Z . Genome-wide analysis of polymerase III-transcribed elements suggests cell-type-specific enhancer function. Genome Res. 2019; 29(9):1402-1414. PMC: 6724667. DOI: 10.1101/gr.249789.119. View

Yates A, Achuthan P, Akanni W, Allen J, Allen J, Alvarez-Jarreta J . Ensembl 2020. Nucleic Acids Res. 2019; 48(D1):D682-D688. PMC: 7145704. DOI: 10.1093/nar/gkz966. View

Panda A, De S, Grammatikakis I, Munk R, Yang X, Piao Y . High-purity circular RNA isolation method (RPAD) reveals vast collection of intronic circRNAs. Nucleic Acids Res. 2017; 45(12):e116. PMC: 5499592. DOI: 10.1093/nar/gkx297. View

Fiszbein A, Krick K, Begg B, Burge C . Exon-Mediated Activation of Transcription Starts. Cell. 2019; 179(7):1551-1565.e17. PMC: 7351029. DOI: 10.1016/j.cell.2019.11.002. View

Zhang Y, Zhang X, Chen T, Xiang J, Yin Q, Xing Y . Circular intronic long noncoding RNAs. Mol Cell. 2013; 51(6):792-806. DOI: 10.1016/j.molcel.2013.08.017. View

Avgan N, Wang J, Fernandez-Chamorro J, Weatheritt R . Multilayered control of exon acquisition permits the emergence of novel forms of regulatory control. Genome Biol. 2019; 20(1):141. PMC: 6637531. DOI: 10.1186/s13059-019-1757-5. View

Ivanov A, Memczak S, Wyler E, Torti F, Porath H, Orejuela M . Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep. 2015; 10(2):170-7. DOI: 10.1016/j.celrep.2014.12.019. View

10.

Ragan C, Goodall G, Shirokikh N, Preiss T . Insights into the biogenesis and potential functions of exonic circular RNA. Sci Rep. 2019; 9(1):2048. PMC: 6376117. DOI: 10.1038/s41598-018-37037-0. View

11.

Ashwal-Fluss R, Meyer M, Pamudurti N, Ivanov A, Bartok O, Hanan M . circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014; 56(1):55-66. DOI: 10.1016/j.molcel.2014.08.019. View

12.

Dong R, Ma X, Chen L, Yang L . Increased complexity of circRNA expression during species evolution. RNA Biol. 2016; 14(8):1064-1074. PMC: 5680680. DOI: 10.1080/15476286.2016.1269999. View

13.

Piwecka M, Glazar P, Hernandez-Miranda L, Memczak S, Wolf S, Rybak-Wolf A . Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 2017; 357(6357). DOI: 10.1126/science.aam8526. View

14.

Irimia M, Blencowe B . Alternative splicing: decoding an expansive regulatory layer. Curr Opin Cell Biol. 2012; 24(3):323-32. DOI: 10.1016/j.ceb.2012.03.005. View

15.

Cheetham S, Faulkner G, Dinger M . Overcoming challenges and dogmas to understand the functions of pseudogenes. Nat Rev Genet. 2019; 21(3):191-201. DOI: 10.1038/s41576-019-0196-1. View

16.

Sterne-Weiler T, Weatheritt R, Best A, Ha K, Blencowe B . Efficient and Accurate Quantitative Profiling of Alternative Splicing Patterns of Any Complexity on a Laptop. Mol Cell. 2018; 72(1):187-200.e6. DOI: 10.1016/j.molcel.2018.08.018. View

17.

Salzman J, Gawad C, Wang P, Lacayo N, Brown P . Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012; 7(2):e30733. PMC: 3270023. DOI: 10.1371/journal.pone.0030733. View

18.

Barbosa-Morais N, Irimia M, Pan Q, Xiong H, Gueroussov S, Lee L . The evolutionary landscape of alternative splicing in vertebrate species. Science. 2012; 338(6114):1587-93. DOI: 10.1126/science.1230612. View

19.

Reyes A, Anders S, Weatheritt R, Gibson T, Steinmetz L, Huber W . Drift and conservation of differential exon usage across tissues in primate species. Proc Natl Acad Sci U S A. 2013; 110(38):15377-82. PMC: 3780897. DOI: 10.1073/pnas.1307202110. View

20.

You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G . Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci. 2015; 18(4):603-610. PMC: 4376664. DOI: 10.1038/nn.3975. View