Integrative transcriptome sequencing reveals extensive alternative trans-splicing and cis-backsplicing in human cells
Journal
Nucleic Acids Research
Journal Volume
46
Journal Issue
7
Pages
3671-3691
Date Issued
2018
Author(s)
Trees-Juen Chuang
Yen-Ju Chen
Chia-Ying Chen
Yi-Da Wang
Chung-Shu Yeh
Min-Yu Yang
Yu-Ting Hsiao
Tien-Hsien Chang
Tzu-Chien Kuo
Hsin-Hua Cho
Chia-Ning Shen
Hung-Chih Kuo
Mei-Yeh Lu
Yi-Hua Chen
Shan-Chi Hsieh
Tai-Wei Chiang
Abstract
Transcriptionally non-co-linear (NCL) transcripts can originate from trans-splicing (trans-spliced RNA; 'tsRNA') or cis-backsplicing (circular RNA; 'circRNA'). While numerous circRNAs have been detected in various species, tsRNAs remain largely uninvestigated. Here, we utilize integrative transcriptome sequencing of poly(A)- and non-poly(A)-selected RNA-seq data from diverse human cell lines to distinguish between tsRNAs and circRNAs. We identified 24,498 NCL events and found that a considerable proportion (20-35%) of them arise from both tsRNAs and circRNAs, representing extensive alternative trans-splicing and cis-backsplicing in human cells. We show that sequence generalities of exon circularization are also observed in tsRNAs. Recapitulation of NCL RNAs further shows that inverted Alu repeats can simultaneously promote the formation of tsRNAs and circRNAs. However, tsRNAs and circRNAs exhibit quite different, or even opposite, expression patterns, in terms of correlation with the expression of their co-linear counterparts, expression breadth/abundance, transcript stability, and subcellular localization preference. These results indicate that tsRNAs and circRNAs may play different regulatory roles and analysis of NCL events should take the joint effects of different NCL-splicing types and joint effects of multiple NCL events into consideration. This study describes the first transcriptome-wide analysis of trans-splicing and cis-backsplicing, expanding our understanding of the complexity of the human transcriptome.
Subjects
MESSENGER-RNA PRECURSORS; CIRCULAR RNAS; SYSTEMATIC IDENTIFICATION; EXON CIRCULARIZATION; CIRCRNA BIOGENESIS; GENE-EXPRESSION; STEM-CELLS; IN-VITRO; ABUNDANT; DROSOPHILA
Publisher
Oxford University Press ({OUP})
Type
journal article