In a Nature paper published online in advance this week, an international team led by investigators at the Cancer Research UK Cambridge Institute shows that "oncogene-induced Nrf2 transcription promotes ROS [reactive oxygen species] detoxification and tumorigenesis." More specifically, by investigating ROS metabolism "in primary murine cells following the expression of endogenous oncogenic alleles of Kras, Braf and Myc," the team observed that those oncogenes actively suppressed the ROS. "K-RasG12D, B-RafV619E, and MycERT2 each increased the transcription of Nrf2," the team writes, adding that "oncogene-directed increased expression of Nrf2 is a new mechanism for the activation of the Nrf2 antioxidant program, and is evident in primary cells and tissues of mice expressing K-RasG12D and B-RafV619E, and in human pancreatic cancer."
The University of California, Berkeley's Xiaohui Qu et al. this week report their use of a single-molecule optical tweezers-based assay on mRNA hairpins, with which they observed that "the translation rate of identical codons at the decoding center is greatly influenced by the GC content of folded structures at the mRNA entry site." The team also found that by applying force to the ends of the hairpin, the translation rate increased. In its quantitative analysis of the force-dependence of its helicase activity, the team found that the ribosome, "unlike previously studied helicases, uses two distinct active mechanisms to unwind mRNA structure," both of which it details in a paper published online in advance in Nature this week.
Investigators at the San Raffaele Scientific Institute in Milan report in a recent Nature advance online publication that a minimal set of three transcription factors "are able to generate directly functional dopaminergic neurons from mouse and human fibroblasts without reverting to a progenitor cell stage." These factors — Mash1, Nurr1, and Lmx1a — can "elicit dopaminergic neuronal conversion in prenatal and adult fibroblasts from healthy donors and Parkinson’s disease patients," the authors write, adding that the "direct generation of iDA [induced dopaminergic] cells from somatic cells might have significant implications for understanding critical processes for neuronal development, in vitro disease modeling, and cell replacement therapies."
Over in Nature Genetics, an international team led by researchers at Seoul National University reports its deep-sequencing and correlation of 18 genome and 17 transcriptomes of unrelated Korean individuals. In mapping both common and rare variants shared among the individuals genome-wide, the team found several variants that were not previously annotated as well as "1,809 sites of transcriptional base modification, where the transcriptional landscape is different from the corresponding genomic sequence, and 580 sites of allele-specific expression." Overall, the authors say that their "findings suggest that a considerable number of unexplored genomic variants still remain to be identified in the human genome."