Afaf El-Sagheer and Tom Brown at the University of Southampton describe in this week's PNAS Early Edition a method for synthesizing chemically modified RNA constructs using click chemistry and solid-phase synthesis "to produce catalytically active hairpin ribozymes around 100 nucleotides in length." The authors suggest that "the ability to synthesize long RNA strands by a combination of solid-phase synthesis and click ligation is an important addition to RNA chemistry."
In another PNAS Early Edition paper, investigators at Stanford and their colleagues at the University of Cambridge report a technique for "non-invasive molecular imagine of c-Myc activation in living mice." Hua Fan-Minogue et al. write that their method uses "a split Firefly luciferase (FL) complementation strategy to detect and quantify the phosphorylation-mediated interaction between glycogen synthase kinase 3β (GSK3β) and c-Myc," adding that "this sensor system consists of two fusion proteins, GSK 35–433-CFL and NFL-c-Myc, in which specific fragments of GSK3β and c-Myc are fused with C-terminal and N-terminal fragments of the split FL, respectively." In this way, the sensor detects the inhibition of c-Myc through differential pathways, the authors show.
Investigators at the National Institute of Mental Health this week report that "common genetic variation in Neuregulin 3 (NRG3) influences risk for schizophrenia and affects NRG3 expression in human brain." In examining 350 families with affected offspring, the authors found a significant association of three SNPs at the intron 1 of NRG3 — rs10883866, rs10748842, and rs6584400 — with an increased risk for schizophrenia. The team's subsequent "molecular cloning and cDNA sequencing in human brain revealed that NRG3 undergoes complex splicing, giving rise to multiple structurally distinct isoforms." Then, using RNA expression profiling of these isoforms in 400 individuals, the team found that "NRG3 expression is developmentally regulated and pathologically increased in schizophrenia."
Researchers in Italy and Spain this week show that "miR-204 is required for lens and retinal development via Meis2 targeting." The investigators demonstrate that abnormally elevated levels of Meis2 resulting from miR-204 inactivation, when combined with the altered regulation of the Pax6 pathway, is "largely responsible" for an "eye phenotype characterized by microphthalmia, abnormal lens formation, and altered dorsoventral patterning of the retina," they write.
In addition PNAS editor-in-chief Randy Schekman unveils PNAS Plus, an online repository for peer-reviewed research articles. "Beginning in January 2011, PNAS will consider Direct Submission manuscripts for exclusive publication online," the editorial team writes, adding that authors will be able to submit up to 10 pages (the current limit is six), and will not be charged an additional fee for color images. "With this dramatic change, we plan a gradual shift in the content of the PNAS print version. PNAS Plus authors will be asked to contribute a one- to two-page summary statement of their work written with the broad readership of the journal in mind," which will appear online as well as in print. The team writes that if the PNAS Plus experiment succeeds, they "envision transitioning to a print edition of PNAS in a magazine format comprising special features, commentaries on important papers flagged by member editors and the editorial board, and summary statements of the online articles." See the entire announcement, here.