UMMS Affiliation

Program in Bioinformatics and Integrative Biology; RNA Therapeutics Institute; Program in Molecular Medicine; Department of Molecular, Cell and Cancer Biology; Department of Biochemistry and Molecular Pharmacology

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Document Type



Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Cell and Developmental Biology | Computational Biology | Genetics and Genomics


Recursive splicing (RS) is an evolutionarily conserved process of removing long introns via multiple steps of splicing. It was first discovered in Drosophila and recently proven to occur also in humans. The detailed mechanism of recursive splicing is not well understood, in particular, whether it is kinetically coupled with transcription. To investigate the dynamic process that underlies recursive splicing, we systematically characterized 342 RS sites in three human cell types using published time-series data that monitored synchronized Pol II elongation and nascent RNA production with 4-thiouridine labeling. We found that half of the RS events occurred post-transcriptionally with long delays. For at least 18-47% RS introns, we detected RS junction reads only after detecting canonical splicing junction reads, supporting the notion that these introns were removed by both recursive splicing and canonical splicing. Furthermore, the choice of which splicing mechanism was used showed cell type specificity. Our results suggest that recursive splicing supplements, rather than replaces, canonical splicing for removing long introns.


Introns, RNA sequencing, Sequence motif analysis, RNA splicing, DNA transcription, Neurons, Exon mapping, Sequence alignment

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Copyright: © 2018 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version



PLoS Genet. 2018 Aug 27;14(8):e1007579. doi: 10.1371/journal.pgen.1007579.eCollection 2018 Aug. Link to article on publisher's site

Journal/Book/Conference Title

PLoS genetics

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PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.