miRNA-132’s Role as a Dynamic Regulator of Memory

Introduction MicroRNAs (miRNAs) are small (~22 nt) evolutionarily-conserved single stranded RNA species that function as potent negative regulators of gene expression (Ambros 2004; Bartel 2004; Lim et al. 2005). miRNAs repress gene expression via their ability to hybridize with the 3’ UTR of target mRNAs, and, in turn, trigger mRNA degradation and/or translational repression (reviewed in (Bartel 2009; Eulalio et al. 2008; Carthew and Sontheimer 2009)). miRNA expression is often cell-type and tissue-specific (Lagos-Quintana et al. 2002; Kim et al. 2004b; Kosik 2006; Cao et al. 2006), and within the central nervous system (CNS), recent work has indicated that they play key roles in a wide range of physiological processes. Along these lines, during development, the disruption of miRNA expression through genetic deletion of Dicer results in aberrant neuronal development and differentiation, as well as altered morphogenesis and neuronal signaling (Cuellar et al. 2008; Giraldez et al. 2005). Furthermore, recent work reveals specific roles for miRNAs (including miR-124a, miR-134 and miR-375) in dendritogenesis and axonal path finding (Schratt et al. 2006; Abdelmohsen et al. 2010; Fiore et al. 2009; Sanuki et al. 2011). As more neuronal-enriched miRNA have been identified, the possibility of a prominent role for miRNA in the regulation of neuronal activity and cognition has emerged (Konopka et al. 2011; Im et al. 2010). Among these is the CREB-regulated miRNA132 (miR-132) (Cheng et al. 2007; Remenyi et al. 2010; Wibrand et al. 2010; Nudelman et al. 2010). miR-132 is transcribed from the intron