Chimerism: A whole new perspective in gene regulation

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 3; p. 130767
• Main Authors: Chitale, Gayatri G., Kulkarni, Shweta R., Bapat, Sharmila A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2025
• Subjects: Animals; Chimerism; Chromosomal rearrangements; Cis/trans chimeras; data collection; evolution; Frameshift; Gene Expression Regulation; genes; Higher order structures; Humans; physiology; protein isoforms; Readthrough; sequence analysis; AFE; Chromosomal rearrangements; ORF; lncRNA; SAS; Higher order structures; MHC; mRNA; Alu; CTCF; RRM; ADP; F-circRNAs; G4; ncRNAs; ASD; UTR; Frameshift; RNA-seq; Cis-SAGe; Cis/trans chimeras; SHS; Ts; DSBs; RNAi; CTs; TEs; NMD; Readthrough; TAD; m6A; ALE; ATP
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2025.130767

The diversity of molecular entities emerging from a single gene are recognized. Several studies have thus established the cellular role(s) of transcript variants and protein isoforms. A step ahead in challenging the central dogma towards expanding molecular diversity is the identification of fusion genes, chimeric transcripts and chimeric proteins that harbor sequences from more than one gene. The mechanisms for generation of chimeras largely follow similar patterns across all levels of gene regulation but also have interdependence and mutual exclusivity. Whole genome and RNA-seq technologies supported by development of computational algorithms and programs for processing datasets have increasingly enabled the identification of fusion genes and chimeric transcripts, while the discovery of chimeric proteins is as yet more subtle. Earlier thought to be associated with cellular transformation, the contribution of chimeric molecules to normal physiology is also realized and found to influence the expression of their parental genes and regulate cellular pathways. This review offers a collective and comprehensive overview of cellular chimeric entities encompassing the mechanisms involved in their generation, insights on their evolution, functions in gene regulation and their current and novel clinical applications. [Display omitted] •Fusion genes, transcripts and proteins harbor sequences from multiple genes.•Mechanisms of chimera formation at all levels of gene regulation follow similar patterns.•Chimeras contribute to disease as well as normal physiology, by influencing parental gene expression and regulation of cellular pathways.•Chimeras contribute to genetic diversity and undergo directional changes in the course of evolution.•These are likely to have prognostic and therapeutic applications.