BACKGROUND: Recent work has identified that many long mRNA-like noncoding RNAs 
(lncRNAs) are expressed in the developing nervous system. Despite their 
abundance, the function of these ncRNAs has remained largely unexplored. We have 
investigated the highly abundant lncRNA RNCR2 in regulation of mouse retinal 
cell differentiation.
RESULTS: We find that the RNCR2 is selectively expressed in a subset of both 
mitotic progenitors and postmitotic retinal precursor cells. ShRNA-mediated 
knockdown of RNCR2 results in an increase of both amacrine cells and Müller 
glia, indicating a role for this lncRNA in regulating retinal cell fate 
specification. We further report that RNCR2 RNA, which is normally 
nuclear-retained, can be exported from the nucleus when fused to an IRES-GFP 
sequence. Overexpression of RNCR2-IRES-GFP phenocopies the effects of 
shRNA-mediated knockdown of RNCR2, implying that forced mislocalization of RNCR2 
induces a dominant-negative phenotype. Finally, we use the IRES-GFP fusion 
approach to identify specific domains of RNCR2 that are required for repressing 
both amacrine and Müller glial differentiation.
CONCLUSION: These data demonstrate that the lncRNA RNCR2 plays a critical role 
in regulating mammalian retinal cell fate specification. Furthermore, we present 
a novel approach for generating dominant-negative constructs of lncRNAs, which 
may be generally useful in the functional analysis of this class of molecules.