DELETION OF 3'-UNTRANSLATED REGION ALTERS THE LEVEL OF MESSENGER-RNA 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 si nce NF mRNA levels are down-regulated after nerve transection. This st udy shows that both postnatal upregulation and axotomy-induced down-re gulation are altered by deletion of 3'-UTR from the mouse Light NF sub unit (NF-L). Transgenes with (NF-L(+)) or without (NF-L(-)) 3'-UTR dis play similar patterns of neuron-specific expression but differ in thei r 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 NP-L expression during postnatal up-regulation and axotomy-induced down-reg ulation. Specifically, the NF-L(-) transgene undergoes a 3-fold aberra nt 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 severalfol d stabilization of NF-L mRNA and an increase in steady-state mRNA leve l. The findings support the working hypothesis that the 3'-UTR contain s determinants that alter stability and that stabilization of NF-L mRN A regulates the levels of NF-L mRNA in neuronal tissues and cells.