Evidence of constraint in the 3D genome for trans-splicing in human cells  

作　　者：Cong Liu Yiqun Zhang Xiaoli Li Yan Jia Feifei Li Jing Li Zhihua Zhang 

机构地区：[1]CAS Key Laboratory of Genome Sciences and Information,Beijing Institute of Genomics,and China National Center for Bioinformation,Chinese Academy of Sciences,Beijing 100101,China [2]School of Life Science,University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Science China(Life Sciences)》2020年第9期1380-1393,共14页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(31671342,31871331,91540114,and 31401112)。

摘　　要：Fusion transcripts are commonly found in eukaryotes, and many aberrant fusions are associated with severe diseases, including cancer. One class of fusion transcripts is generated by joining separate transcripts through trans-splicing. However, the mechanism of trans-splicing in mammals remains largely elusive. Here we showed evidence to support an intuitive hypothesis that attributes trans-splicing to the spatial proximity between premature transcripts. A novel trans-splicing detection tool(TSD) was developed to reliably identify intra-chromosomal trans-splicing events(i TSEs) from RNA-seq data. TSD can maintain a remarkable balance between sensitivity and accuracy, thus distinguishing it from most state-of-the-art tools. The accuracy of TSD was experimentally demonstrated by excluding potential false discovery from mosaic genome or template switching during PCR. We showed that i TSEs identified by TSD were frequently found between genomic regulatory elements, which are known to be more prone to interact with each other. Moreover, i TSE sites may be more physically adjacent to each other than random control in the tested human lymphoblastoid cell line according to Hi-C data. Our results suggest that trans-splicing and 3 D genome architecture may be coupled in mammals and that our pipeline, TSD, may facilitate investigations of trans-splicing on a systematic and accurate level previously thought impossible.

关 键 词：TRANS-SPLICING chromatin interaction 3D genome spatial clustering 

分 类 号：R394[医药卫生—医学遗传学]