Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation.

MLL5 is a divergent member of the Drosophila Trithorax-related (SET) domain and plant homeodomain (PHD) domain-containing chromatin regulators that are involved in the regulation of transcriptional "memory" during differentiation. Human MLL5 is located on chromosome 7q22, which frequently is deleted in myeloid leukemias, suggesting a possible role in hemopoiesis. To address this question, we generated a loss-of-function allele (Mll5(tm1Apa)) in the murine Mll5 locus.

Identification of c-myc coding region determinant RNA sequences and structures cleaved by an RNase1-like endoribonuclease.

The coding region of c-myc mRNA encompassing the coding region determinant (CRD) nucleotides (nts) 1705-1792 is critical in regulating c-myc mRNA stability. This is in part due to the susceptibility of c-myc CRD RNA to attack by an endoribonuclease. We have previously purified and characterized a mammalian endoribonuclease that cleaves c-myc CRD RNA in vitro.

Destroying RNA as a therapeutic approach.

The ability to target RNA, mRNA and viral RNA in particular, for degradation is a powerful approach in molecular biology and pharmacology. Such approaches can be used in the study of gene function as in functional genomics, in the identification of disease-associated genes, and for the treatment of human diseases. This review provides a comprehensive up-to-date look at all the current available technologies used for the destruction of RNA, with a focus on their therapeutic potential.

Purification and characterization of a novel mammalian endoribonuclease.

Endonuclease-mediated mRNA decay appears to be a common mode of mRNA degradation in mammalian cells, but yet only a few mRNA endonucleases have been described. Here, we report the existence of a second mammalian endonuclease that is capable of cleaving c-myc mRNA within the coding region in vitro. This study describes the partial purification and biochemical characterization of this enzyme.