homology with DNA methyltransferase, the Drosophila trithorax gene product, and the "AT-hook" motif of high-mobility-group proteins. An alternative splice that deletes the AT-hook region of MLL was identified. AF4 is a serine-and proline-rich putative transcription factor with a glutamine-rich carboxyl terminus. The composition of the complete MLL-AF4 fusion product argues that it may act through either a gain-of-function or a dominant negative mechanism in leukemogenesis.

No abstract

The MLL gene is involved in translocations associated with both acute lymphoblastic and acute myelogenous leukemia. These translocations fuse MLL with one of over 30 partner genes. Collectively, the MLL partner genes do not share a common structural motif or biochemical function. We have identified a protein interaction between the two most common MLL fusion partners AF4 and AF9. This interaction is restricted to discrete nuclear foci we have named 'AF4 bodies'. The AF4 body is non-nucleolar and is not coincident with any known nuclear structures we have examined. The AF4-AF9 interaction is maintained by the MLL-AF4 fusion protein, and expression of the MLL-AF4 fusion can alter the subnuclear localization of AF9. In view of other research indicating that other MLL fusion partners also interact with one another, these results suggest that MLL fusion partners may participate in a web of protein interactions with a common functional goal. The disruption of this web of interactions by fusion with MLL may be important to leukemogenesis.

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Recently, by genetic and biochemical approaches, it has been shown that adenovirus VAI RNA is required for efficient translation of viral mRNAs at late times after infection. To understand the nucleotide sequences and the domains of the VAI RNA that are responsible for the role of VAI RNA in enhancement of translation, a mutational analysis of the VAI gene was undertaken. Deletion, substitution, and insertion mutations covering most of the nucleotide sequences of VAI RNA were introduced into the VAI gene at the plasmid level. These mutant genes were then reintroduced into the virus, and growth properties of the mutant viruses were studied. The majority of the mutants retained normal or nearly normal levels of biological function. Mutations in the region between +43 and +53 and between +107 and the 3' end of the gene resulted in a considerable loss of activity. These mutants, however, grew significantly better than did an adenovirus type 5 mutant lacking both functional VAI and VAII genes, indicating that they retain a portion of their activity. Because no one mutation was able to completely abolish the function, we suggest that the VAI RNA may have multiple functional sites for its translation modulation function. These multiple sites may be short oligonucleotide sequences that may interact with cellular or viral components or both during translation.Adenoviruses synthesize large amounts of two low-molecular-weight RNAs designated VAI and VAII (20,23). The genes coding for these two RNAs are located between 29.0 and 31.0 map units (m.u.) on the adenoviral chromosome. Nucleotide sequences of these RNAs have been determined (1,19,25). The virus-associated (VA) RNA genes are transcribed by RNA polymerase III (23,31). An intragenic transcription control region for the VAI gene has been identified, and it maps between +10 and +69 (4, 8, 12) (the numbering here and throughout this article is relative to the starting point of the VAI-G RNA). In the infected cells, a cellular phosphoprotein of 45,000 molecular weight has been shown to be associated with VA RNAs, and the nucleoprotein complex is recognized by the anti-La class of lupus sera (9,13,14 30.0 m.u.) cloned between the PvuII and EcoRI sites of pBR322. Plasmids were propagated in Escherichia coli HB101.Mutagenesis of VAI gene. Substitution and insertion mutations located in the 5' half of the gene were constructed with HindIII linkers as described in an earlier report (4). Deletion mutations in the 3' half of the molecule were obtained by the D-loop mutagenesis procedure (11,22). A 53-bp deletion in 187 on May 11, 2018 by guest