ELAV tumor antigen, Hel-N1, increases translation of neurofilament M mRNA and induces formation of neurites in human teratocarcinoma cells

Human ELAV proteins are implicated in cell growth and differentiation via r egulation of mRNA expression in the cytoplasm. In human embryonic teratocar cinoma (hNT2) cells transfected with the human neuronal ELAV-Iike protein, Hel-N1, neurites formed, yet cells were not terminally differentiated. Cell s in which neurite formation was associated with Hel-N1 overexpression, als o expressed increased levels of endogenous neurofilament M (NF-M) protein, which distributed along the neurites. However, steady-state levels of NP-M mRNA remained similar whether or not hNT2 cells were transfected with Hel-N 1. These findings suggest that turnover of NF-M mRNA was not affected by He l-N1 expression, despite the fact that Hel-N1 can bind to the 3' UTR of NF- M mRNA and was found directly associated with NF-M mRNA in transfected cell s. Analysis of the association of NF-M mRNA with the translational apparatu s in Hel-N1 transfectants showed nearly complete recruitment to heavy polys omes, indicating that Hel-N1 caused an increase in translational initiation . Our results suggest that the stability and/or translation of ARE-containi ng mRNAs can be regulated independently by the ELAV protein, Hel-N1, depend ing upon sequence elements in the 3' UTRs and upon the inherent turnover ra tes of the mRNAs that are bound to Hel-N1 in vivo.