Ming Zhan

We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addition, there are isolated contigs that we believe represent nonrepetitive pockets within the heterochromatin of the centromeres. Comparison with a previously sequenced 2.9- megabase region indicates that sequencing accuracy within nonrepetitive segments is greater than 99. 99% without manual curation. As such, this initial reconstruction of the Drosophila sequence should be of substantial value to the scientific community.

Previous studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis, are resistant to radiation and chemotherapy, and contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSCs. Here, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24(-)CD44(+) are primarily quiescent and localized at the tumor invasive front, whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH), are proliferative, and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer, and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination, and growth at metastatic sites.

HuR, a protein that binds to specific mRNA subsets, is increasingly recognized as a pivotal posttranscriptional regulator of gene expression. Here, HuR was immunoprecipitated under conditions that preserved HuR-RNA interactions, and HuR-bound target mRNAs were identified by cDNA array hybridization. Analysis of primary sequences and secondary structures shared among HuR targets led to the identification of a 17- to 20-base-long RNA motif rich in uracils. This HuR motif was found in almost all mRNAs previously reported to be HuR targets, was located preferentially within 3′ untranslated regions of all unigene transcripts examined, and was conserved in >50% of human and mouse homologous genes. Importantly, the HuR motif allowed the successful prediction and subsequent validation of novel HuR targets from gene databases. This study describes an HuR target RNA motif and presents a general strategy for identifying target motifs for RNA-binding proteins.