Female Reproduction
Rong Li, Francesco J. DeMayo, in Encyclopedia of Reproduction (Second Edition), 2018
Isoforms
Protein isoforms are generated from the same gene but with distinct amino acid sequences and biological roles (Gunning, 2006). Alternative promoter, splicing and translation initiation sites are common mechanisms of producing protein isoforms (Chen and Manley, 2009; Pal et al., 2011; Kochetov, 2008), and are identified in SRs.
Multiple promoters reside at SR genes. At a minimum, the number of promoters is eleven for ESR1 (Kos et al., 2001; Zou et al., 2009; Okuda et al., 2003), four for ESR2 (Hirata et al., 2001; Shoda et al., 2002; Smith et al., 2010; Lee et al., 2013), five for PGR (Yamanaka et al., 2002; Hirata et al., 2000, 2002; Saner et al., 2003; Kastner et al., 1990), nine for GR (Palma-Gudiel et al., 2015; Breslin et al., 2001; Turner and Muller, 2005; Presul et al., 2007) and two for MR (Zennaro et al., 1995), but only one identified for AR so far (Ahrens-Fath et al., 2005; Dehm et al., 2008; Tilley et al., 1990).
Coupling with the multiple promoters, alternative splicing produces dozens of transcription isoforms by intron/exon skipping, inserting, or replicating. Many SR transcription isoforms have been demonstrated with physiological and/or pathological functions, such as ERβcx (Herynk and Fuqua, 2004), PGR-C, -M, -S (Wei et al., 1990; Cork et al., 2008), AR-V7, -V9 (Lu et al., 2015; Dehm and Tindall, 2011), GRγ, GR-A and GR-P(Moalli et al., 1993; Ray et al., 1996), and MR248, MR260, MR+4 (Bloem et al., 1995; Zennaro et al., 2001) etc.
Alternative translation further increases the number of protein isoforms. For example, 8 alternative translation initiation sites (TIS) have been identified in GR, thus 8 translation isoforms could be generated from a single GR transcription isoform, such as GRα and β (Lu and Cidlowski, 2005). In the same paper, the authors predict more species conserved TIS at the N-terminal of ESR1, PGR, AR, and MR (Lu and Cidlowski, 2005). Several of these internal TIS have already been identified as truly functional alternative translational start sites (Pascual-Le Tallec et al., 2004; Barraille et al., 1999; Wilson and McPhaul, 1994; Chantalat et al., 2016).