Mechanisms of retrocopy promoter acquisition. Schematic representations (A,C,E,G) and examples (B,D,F,H) of retrocopy promoter gain mechanisms. In A,C,E,G, the gene structures are depicted as thick boxes (coding exons/exon parts), thin boxes (UTRs), and connecting lines (introns). In A,C,E,G, the upper part shows the genomic locus before (A,C,E) or upon (G) the retrocopy integration; the lower part shows the locus after the gain/recruitment of the retrocopy promoter. B,D,F,H show (from top to bottom) the RNA-seq coverage (all reads from all samples); the location of CAGE peaks; the assembled retrocopy transcript(s), with exons defined by blue boxes and introns as blue lines; and the original retrocopy locus (coding part). (A) A parental gene transcript generated from an upstream promoter carries an alternative downstream promoter from which the retrocopy will be expressed. (B) The hsa_retrop24247 human retrocopy promoter corresponds to a parentally inherited sequence (thin black box), suggesting that an alternative parental promoter was present in the retrotransposed mRNA. (C) Retrocopy integration into a host gene and generation of a chimeric transcript through splicing. (D) The mus_retrop52885 mouse retrocopy (Taf9) expresses three alternative chimeric transcripts containing exons of its host gene Ak6. The three isoforms are generated by alternative transcription start sites as indicated by the presence of multiple CAGE peaks. (E) Retrocopy expression driven by the bidirectional promoter of an upstream gene. (F) The hsa_retrop09498 (HTR7P1) human retrocopy promoter has been recruited from the neighboring gene HEBP1. (G) Retrocopy integration in proximity to a proto-promoter sequence, which will evolve as a novel retrocopy promoter. (H) The hsa_retrom15096 (SEPHS2) human retrocopy promoter overlaps a CpG island (purple box) not associated to any other gene, indicating that this sequence has been recruited or evolved as a putative novel promoter. (I) Relative contribution of promoter acquisition mechanisms in human and mouse retrocopies.
