fusionsplicings

Fusionsplicings is a term used to describe a class of RNA splicing events that produce chimeric transcripts by fusing sequences from two distinct gene loci. These events can occur as RNA-level trans-splicing between separate pre-mRNAs or as a consequence of genomic rearrangements that generate a single transcription unit containing exons from different genes. In practice, fusionsplicings results are detected as splice junctions that connect exons from different genomic origins within a single RNA molecule.

Mechanistically, fusionsplicings can arise through several pathways. Trans-splicing combines exons from two separate precursor RNAs during or after transcription, with the spliceosome recognizing mixed donor and acceptor sites. Alternatively, a chromosomal rearrangement such as a translocation or inversion can create a fusion gene whose mature mRNA is spliced to yield a continuous chimeric transcript. In some cases, complex alternative splicing across neighboring or overlapping genes can also generate similar fusion-like transcripts. The functional impact of fusionsplicings ranges from neutral or degradable transcripts to those encoding novel proteins with altered domains or regulatory properties.

Occurrence and significance vary by organism and tissue. Fusion transcripts have been observed in normal development and in various cancers, where they can act as drivers, biomarkers, or sources of neoantigens. Their biological relevance depends on the stability of the transcript, the integrity of the open reading frame, and the functional contribution of partner gene domains.

Detection and analysis rely on high-throughput sequencing and validation methods. RNA sequencing with junction-aware alignment, specialized fusion-detection tools, and long-read sequencing help identify candidate fusionsplicings, which are typically validated by RT-PCR and Sanger sequencing. Challenges include distinguishing true fusion events from mapping artifacts, repetitive regions, and highly similar gene families.

See also: trans-splicing, gene fusion, alternative splicing, RNA-seq.