News & Comment

Activation of STAT3-coupled receptors along with TGF-β signaling are fundamental for Th17 cell differentiation both in vivo and in vitro. A recent paper shows that TGF-β signaling relieves SKI-mediated transcriptional repression of Rorc, the key regulator of the Th17 program.

Wild mice are genetically similar to laboratory mice, but have a distinct gut microbiota that protects from disease.

Two articles in Cell Research focus on the structure-function relationships in the shelterin complex that binds to telomeres and is essential for their stability and functions. These studies concerning both mammalian and Schizosaccharomyces pombe proteins reveal unexpected structural conservation of a motif called TRFH (Telomeric Repeat Factors Homology) domain between several subunits in these complexes, providing a rationale for further dissection of the role of telomeres in chromosome stability, aging and cancer, and encouraging us to revisit the evolution of telomere proteins.

Avian influenza A H7N9 viruses that emerged in China in 2013 have reappeared each year, causing more than 1 600 severe human infections. As these viruses have evolved in nature, they have gained some and can gain additional virulence determinants that enhance their risk for humans, underlining the urgent need to control and eradicate H7N9 viruses in China.

B cells undergo stringent selection in germinal centers (GCs) for expression of high-affinity antibodies, however, mechanisms of negative selection of low-affinity B cell clones remain elusive. A new study by Michel Nussenzweig's group published in Science leverages a new reporter system that marks pre-apoptotic GC B cells to dissect microanatomic regions of GCs and their role in affinity maturation.

Long-noncoding RNAs (lncRNAs) are emerging as important regulators of cellular processes, but few have been functionally characterized in host-pathogen interactions. A recent report in Science demonstrates a mechanistic role for a novel lncRNA in directly binding an essential metabolic enzyme, glutamic-oxaloacetic transaminase (GOT2); this interaction benefits viral replication via alteration of host metabolism.

Recently, ZATT (also known as ZNF451 or Zpf451) was reported by Schellenberg et al. to aid the removal of Topoisomerase II cleavage complexes by stimulating the phosphodiesterase activity of Tyrosyl DNA Phosphodiesterase 2. Although the full implication of this discovery is unknown, it will help us understand how cells respond to topoisomerase-induced genome damage and chemotherapeutic topoisomerase 'poisons'.

In an elegant publication in Cell Research, Tan and colleagues showed that ablation of PRRT2 in cerebellar granule cells is sufficient to induce paroxysmal kinesigenic dyskinesia. PRRT2 turns out to downregulate the presynaptic SNARE complex in granule cell axons, which in turn controls the activity patterns of Purkinje cells, the sole output of the cerebellar cortex.

In a paper recently published in Cell Research, Yu et al. identify two MAPK-related kinases, MAPK11 and HIPK3, as positive regulators of levels of mutant huntingtin protein, a toxic species highly involved in Huntington's disease (HD) pathology. The identification and validation of these kinases as therapeutic targets for knockdown in multiple relevant experimental model systems reveal novel potential approaches for treatment of HD.

Circular RNAs (circRNAs) are a novel class of RNA whose physiological function has yet to be investigated. A recent publication in Science provides the first evidence of the biological relevance of a circRNA in an in vivo model and unveils an unexpected twist on their crosstalk with miRNAs.

Intermittent fasting (IF) has been shown to promote metabolic health in several organisms. Two recent papers show that IF induces white adipose tissue beiging and increases thermogenesis, which improves metabolic health in mice.

In a recent paper published in Cell Research, a cryo-EM structure reveals the interface between DNA-PKcs and the Ku70/80:DNA complex, together forming the DNA-dependent protein kinase holoenzyme in non-homologous DNA end joining. Insight from this structure suggests how an allosteric rearrangement of DNA-PKcs driven by Ku70/80:DNA binding regulates kinase activity in this largest member of a family of structurally homologous phosphoinositide 3-kinase-related protein kinases that includes mTOR, ATR, and ATM.

In a recent paper published in Cell Research, Abdul-Ghani and colleagues show that the cytokine, cardiotrophin-1 (CT1), drives a protective form of reversible cardiac hypertrophy that acts through a nonapoptotic caspase-dependent mechanism. Since CT1 can be delivered as exogenous protein, these studies provide new biological insights and potential translational opportunities.