In Cell this week, researchers in Spain and Philadelphia used a GENCODE annotations of the human genome to characterize more than 1,000 long noncoding RNAs that are expressed in multiple cell lines, and found an enhancer-like function for a set of the long ncRNAs in human cell lines. "Depletion of a number of ncRNAs led to decreased expression of their neighboring protein-coding genes, including the master regulator of hematopoiesis, SCL (also called TAL1), Snai1 and Snai2," the authors write. These results, the team adds, show an unexpected role for a class of long ncRNAs in the regulation of development and differentiation.
Also in Cell this week, researchers in Massachusetts, New Jersey, and Washington identified aneuploidy yeast strains with improved proliferative abilities and found strain-specific genetic alterations and mutations shared between different aneuploid strains. A loss-of-function mutation in the gene encoding the deubiquitinating enzyme Ubp6 attenuated the changes in intracellular protein composition caused by aneuploidy, thereby improving the growth rate in four different aneuploidy strains, the researchers say. "Our results demonstrate the existence of aneuploidy-tolerating mutations that improve the fitness of multiple different aneuploidies and highlight the importance of ubiquitin-proteasomal degradation in suppressing the adverse effects of aneuploidy," the team adds.
An international team of researchers suggest that activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interacting with Spt5 in Cell this week. The researchers performed an shRNA screen to identify factors required for class switch recombination of antibody loci, and found that Spt5 is required for class switch recombination. "Spt5 interacts with AID, it facilitates association between AID and Pol II, and AID recruitment to its Ig and non-Ig targets. ChIP-seq experiments reveal that Spt5 colocalizes with AID and stalled Pol II," the researchers write. Spt5 accumulation at sites of Pol II stalling is predictive of mutation induced by AID, they add.
Finally, researchers from the US and Australia show that SPCA2 — an isoform of secretory pathway Ca2+-ATPase — is upregulated in breast cancer-derived cells and human breast tumors, and that suppression of SPCA2 attenuates basal Ca2+ levels and tumorigenicity. Unexpectedly, however, the researchers say SPCA2-Orai1 signaling was independent of ER Ca2+ stores or STIM1 and STIM2 sensors and uncoupled from Ca2+-ATPase activity of SPCA2. "Our findings reveal a signaling pathway in which the Orai1-SPCA2 complex elicits constitutive store-independent Ca2+ signaling that promotes tumorigenesis," the team writes.