MBNL2 encodes Muscleblind Like Splicing Regulator 2 which is C3H-type zinc finger protein that modulates alternative splicing of pre-mRNAs (Fig. 1 and Table 3). There is compelling evidence that alcohol and alcohol dependence affect alternative splicing mechanisms of various genes (Sasabe and Ishiura, 2010). For example, alcohol affects pre-mRNA alternative splicing at DRD2 which encodes the dopamine type 2 receptor (Wernicke et al., 2010), NMDA receptor NR1 subunit encoded by GRIN1 that can produce as many as eight spliced variants (Hardy et al., 1999; Honse et al., 2003; Kumari, 2001), and BK channel alpha1 subunit (Pietrzykowski et al., 2008). In addition, altered GABA-B receptor subunit 1 splicing is observed in human alcoholic post-mortem brain (Lee et al., 2014). Thus it can be reasonably hypothesized that genetic variation in MBNL2 may affect alcohol dependence phenotypes by altering alternative splicing mechanisms that are known to contribute to splicing of alcohol-responsive proteins.
