THE POLYRIBOSOMAL PROTEIN-BOUND TO THE 3'-END OF HISTONE MESSENGER-RNA CAN FUNCTION IN HISTONE PRE-MESSENGER-RNA PROCESSING

Cell cycle-regulated histone mRNAs end in a conserved 26-nt sequence t hat can form a stem-loop with a six-base stem and a four-base loop. Th e 3' end of histone mRNA has distinct functions in the nucleus and in the cytoplasm. In the nucleus it functions in pre-mRNA processing and transport, whereas in the cytoplasm it functions in translation and re gulation of histone mRNA stability. The stem-loop binding protein (SLB P), present in both nuclei and polyribosomes, is likely the trans-acti ng factor that binds to the 3' end of mature histone mRNA and mediates its function. A nuclear extract that efficiently processes histone pr e-mRNA was prepared from mouse myeloma cells. The factor(s) that bind to the 3' end of histone mRNA can be depleted from this extract using a biotinylated oligonucleotide containing the conserved stem-loop sequ ence. Using this depleted extract which is deficient in histone pre-mR NA processing, we show that SLBP found in polyribosomes can restore pr ocessing, suggesting that SLBP associates with histone pre-mRNA in the nucleus, participates in processing, and then accompanies the mature mRNA to the cytoplasm.