Abstract
A major part of the transcriptome complexity is attributed to multiple types of DNA or RNA fusion events, which take place within a gene such as alternative splicing or between different genes such as DNA rearrangement and trans-splicing. In the present study, using the RNA deep sequencing data, we systematically survey a type of non-canonical fusions between the RNA transcripts from the two opposite DNA strands. We name the products of such fusion events cross-strand chimeric RNA (cscRNA). Hundreds to thousands of cscRNAs can be found in human normal tissues, primary cells, and cancerous cells, and in other species as well. Although cscRNAs exhibit strong tissue-specificity, our analysis identifies thousands of recurrent cscRNAs found in multiple different samples. cscRNAs are mostly originated from convergent transcriptions of the annotated genes and their anti-sense DNA. The machinery of cscRNA biogenesis is unclear, but the cross-strand junction events show some features related to RNA splicing. The present study is a comprehensive survey of the non-canonical cross-strand RNA junction events, a resource for further characterization of the originations and functions of the cscRNAs.
Highlights
A major part of the transcriptome complexity is attributed to multiple types of DNA or RNA fusion events, which take place within a gene such as alternative splicing or between different genes such as DNA rearrangement and trans-splicing
The detailed machinery of cross-strand chimeric RNA (cscRNA) biogenesis and their potential functions are still unclear, we propose that they represent an additional level of the transcriptome complexity, which is worth further investigation
We developed a bioinformatics pipeline cscMap to search for the cscRNAs, i.e., RNA chimeras resulted from fusions of the transcripts encoded by the two opposite DNA strands (Fig. 1a)
Summary
A major part of the transcriptome complexity is attributed to multiple types of DNA or RNA fusion events, which take place within a gene such as alternative splicing or between different genes such as DNA rearrangement and trans-splicing. Several fusion proteins, for example, BCR-ABL1 in chronic myelogenous leukemia[12] and EML4-ALK in lung cancer[13], serve as effective therapeutic targets[6,14,15] Another type of gene fusion takes place between RNA molecules in the absence of DNA rearrangement, for example, trans-splicing or transcription read-through between two precursor RNAs16. Such non-canonical RNA splicing between different genes is another source of transcriptome complexity[17], which has been frequently reported in both cancerous and normal cell contexts[10,18,19,20,21,22,23]. We ask whether these transcripts could form a different type of chimeric RNAs, which are cross-strand RNA fusion products, i.e., cross-strand chimeric RNAs (cscRNAs)
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