In Science this week, a Cornell University team reports on the results of a study using a precision nuclear run-on and sequencing assay to map the genome-wide distribution of transcriptionally engaged Pol II at base-pair resolution. They found that Pol II accumulates immediately downstream of promoters, at intron-exon junctions that are efficiently used for splicing and over 3′ polyadenylation sites. "Focused analyses of promoters reveal that pausing is not fixed relative to initiation sites, nor is it specified directly by the position of a particular core promoter element or the first nucleosome," the researchers write. Meantime, core promoter elements function "beyond initiation, and when optimally positioned they act collectively to dictate the position and strength of pausing," they add.
Also in Science, a group of National Institutes of Health researchers detail a framework for making decisions about future research with highly pathogenic avian influenza H5N1 viruses. They review two reports from mid-2012 showing that the viruses could be rendered transmissible by respiratory droplets among ferrets, and discuss international talks that led to the creation of the new framework, which calls for any research proposals involving the transmission of HPAI H5N1 among mammals by respiratory droplets to undergo additional review.
Finally in Science, a group of investigators from the University of Basel and from the Institute of Molecular Systems Biology described a new role for the Ser-Thr kinase mammalian target of rapamycin, or mTOR, which controls cell growth and metabolism by stimulating glycolysis, as well as protein and lipid synthesis. They used quantitative phosphoproteomics to identify substrates or downstream effectors of the two mTOR complexes and found that mTOR controlled the phosphorylation of 335 proteins including CAD, which catalyzes the first three steps in de novo pyrimidine synthesis. Further, mTORC1 indirectly phosphorylated CAD-S1859 through S6 kinase, and CAD-S1859 phosphorylation promoted CAD oligomerization and thereby stimulated de novo synthesis of pyrimidines and progression through S phase of the cell cycle in mammalian cells. "Thus, mTORC1 also stimulates the synthesis of nucleotides to control cell proliferation."