ACTIVITY OF A 40 KDA RNA-BINDING PROTEIN CORRELATES WITH MYCN AND C-FOS MESSENGER-RNA STABILITY IN HUMAN NEUROBLASTOMA

Subclones of neuroblastic (N) and substrate adherent (S) cells have be en established from neuroblastoma tumours cultured in vitro which diff er in growth characteristics and MYCN expression. N cells derived from the NBL-W cell line (W-N) express 5-fold higher levels of MYCN mRNA a nd 10-fold higher levels of MYCN protein than S cells (W-S), despite h aving the same MYCN copy number. In an effort to identify the molecula r mechanisms responsible for the disparity in steady-state MYCN levels , the rate of MYCN mRNA degradation was measured in the two subclones. The half-life of MYCN mRNA in the W-N cells was approximately 45 min compared to approximately 6 min in the W-S cells. Similarly, the half- life of another labile mRNA, c-fos, differed in W-N and W-S cells (30 min versus 15 min, respectively). The turnover of labile mRNAs is thou ght to be mediated by the interactions of trans-acting factors with AU -rich elements within the 3' untranslated region. RNA UV cross-linking assays using W-N cell lysate demonstrated abundant quantities of a pr otein, 40 kDa in size (p40), that bound specifically to AU-rich elemen ts within the MYCN and c-fos 3' untranslated region. However, p40 was barely detectable in W-S cells. Our studies suggest that p40 may play a role in determining neuroblastoma phenotype by regulating MYCN and c -fos mRNA turnover. (C) 1997 Published by Elsevier Science Ltd.