Deletion of 3'-untranslated region alters the level of mRNA expression of a neurofilament light subunit transgene.

High levels of neurofilament (NF) mRNA expression are attained during early postnatal development and are a major determinant of axonal size. High level NF expression is also dependent upon axonal continuity since NF mRNA levels are down-regulated after nerve transection. This study shows that both postnatal up-regulation and axotomy-induced down-regulation are altered by deletion of 3'-UTR from the mouse light NF subunit (NF-L). Transgenes with (NF-L+) or without (NF-L-) 3'-UTR display similar patterns of neuron-specific expression but differ in their respective levels of expression. Whereas changes in the level of NF-L+ mRNA parallel those of the endogenous mouse NF-L mRNA, changes in the level of NF-L- mRNA differ from the pattern of endogenous NF-L expression during postnatal up-regulation and axotomy-induced down-regulation. Specifically, the NF-L- transgene undergoes a 3-fold aberrant up-regulation between embryonic days 15 (E15) and 18 (E18) and has lost its susceptibility to axotomy-induced down-regulation. Studies of transfected P19 cells show that 3'-UTR deletion leads to a severalfold stabilization of NF-L mRNA and an increase in steady-state mRNA level. The findings support the working hypothesis that the 3'-UTR contains determinants that alter stability and that stabilization of NF-L mRNA regulates the levels of NF-L mRNA in neuronal tissues and cells.