RNA 3' processing regulates histone mRNA levels in a mammalian cell cycle mutant. A processing factor becomes limiting in G1-arrested cells.

Post-transcriptional regulation of histone gene expression in a mouse mastocytoma cell cycle mutant (21-Tb) depends largely on conserved DNA sequences that are essential for RNA 3' processing. We have analyzed whether this regulation occurs at the level of RNA 3' processing. We show, by RNase mapping, that nuclear H4 mRNA precursors, which are hardly detectable in total RNA from exponentially dividing cells, accumulate in G1-arrested cells, i.e. when mature mRNAs are drastically reduced. Furthermore, we show that a heat-labile component of the processing apparatus, recently identified in HeLa cell nuclear extracts, is limiting in extracts from G1-arrested 21-Tb cells. In contrast, this activity is in excess in extracts from exponentially dividing cells, whereas both extracts contain similar amounts of snRNPs of the Sm serotype. These fluctuations in the heat-labile activity may generally contribute to proliferation or cell cycle dependent histone gene regulation.