In this week's PNAS Early Edition, an international research team led by investigators at the Chung-Ang University College of Medicine in Seoul describe how it induced self-renewal in human somatic progenitor cells in an efficient, safe, and therapeutically effective manner with one "regulatable gene," v-myc. The team created "induced conditional self-renewing progenitor cells" by introducing v-myc via a Tet-on gene expression system. In culture, the team found that Tet activated myc transcription and translation, "allowing efficient expansion of homogeneous, clonal, karyotypically normal human [central nervous system] precursors ex vivo." Conversely, the team found that "in vivo, where Tet was absent, myc was not expressed, and self-renewal was entirely inactivated, as was tumorigenic potential." The researchers suggest that their strategy may also be applicable to other precursor cell types.
A trio of investigators at the Istituto di Biologia Cellulare in Rome this week discusses the "evolution of introns in the archaeal world," in which, the group says, two striking features characterize RNA splicing: the existence self-splicing group I introns and that "all introns are removed by tRNA splicing endonucleases." The team shows that "all known oligomeric structures of the endonuclease can recognize and cleave a ribosomal intron, even when the endonuclease derives from a strain lacking rRNA introns," which it says explains the "persistence of group I introns in mitochondria and chloroplasts," as they are inaccessible to the endonuclease.
Researchers in France suggest in a paper published online in PNAS that a "recurrent, low-level mutation by APOBEC3A could catalyze the transition from a healthy to a cancer genome." More specifically, as human mitochondrial and nuclear DNA are both "vulnerable to somatic hypermutation by A3 deaminases," particularly APOBEC3A, the team suggests that the increased amounts of genomic editing they've observed in patients lacking the uracil DNA-glycolase gene indicate "a dynamic composed of A3 editing and DNA catabolism involving uracil DNA-glycolase."
Also in PNAS this week, researchers at Columbia University and Weill Cornell Medical College report their use of cryoelectron microscopy on ribosomes with a P-loop mutation to identify the structural intermediates that they say may work to regulate the rate of translocation.