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The temporal landscape of recursive splicing during Pol II transcription elongation in human cells

Zhang, Xiao-Ou
Fu, Yu
Mou, Haiwei
Xue, Wen
Weng, Zhiping
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Abstract

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.

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

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DOI
10.1371/journal.pgen.1007579
PubMed ID
30148885
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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.