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

PLoS Genetics
Xiao-Ou ZhangZhiping Weng

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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Citations

Feb 14, 2021·Science China. Life Sciences·Wei XueLi Yang
Apr 23, 2021·Wiley Interdisciplinary Reviews. RNA·John G Conboy
May 11, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Dirk Roos, Martin de Boer
Dec 16, 2021·Human Genetics·Anjani KumariMarzena Wojciechowska
Jan 29, 2022·PloS One·Sohyun Moon, Ying-Tao Zhao

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Methods Mentioned

BETA
total
RNA-seq
PCR
ChIP-seq

Software Mentioned

WebLogo3
SVM
HISAT2
DAVID
RepeatMasker
ENCODE
seq
TERate
BPfinder
Bowtie2

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