Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair.

Various DNA damage response factors form biomolecular condensates at DNA lesions. Targeting phase separation in DNA repair factor assemblies may provide a potential anticancer strategy. An RNA-binding protein, Y14/RBM8A, facilitates the repair of DNA double-strand breaks (DSBs) via its RNA-mediated interaction with non-homologous end joining (NHEJ) factors.

Sculptors of cerebellar fissures and their potential as therapeutic targets for cerebellar dysfunction.

The cerebellum plays an important role in both motor control and cognition. The cerebellar cortex is neuron-rich and composed of characteristic folia and fissures. Defective cerebellar development leads to movement disorders and developmental delay.

RBM4-mediated intron excision of Hsf1 induces BDNF for cerebellar foliation.

Brain-derived neurotrophic factor (BDNF) plays important roles in brain development and neural function. Constitutive knockout of the splicing regulator RBM4 reduces BDNF expression in the developing brain and causes cerebellar hypoplasia, an autism-like feature. Here, we show that Rbm4 knockout induced intron 6 retention of Hsf1, leading to downregulation of HSF1 protein and its downstream target BDNF.

Activation of TrkB signaling mitigates cerebellar anomalies caused by Rbm4-Bdnf deficiency.

A molecular and functional link between neurotrophin signaling and cerebellar foliation is lacking. Here we show that constitutive knockout of two homologous genes encoding the RNA binding protein RBM4 results in foliation defects at cerebellar lobules VI-VII and delayed motor learning in mice. Moreover, the features of Rbm4 double knockout (dKO), including impaired differentiation of cerebellar granule cells and dendritic arborization of Purkinje cells, are reminiscent of neurotrophin deficiency.

Modulates Lifespan and Oxidative Stress Tolerance in .

Altered metabolism is a hallmark of aging. The tricarboxylic acid cycle (TCA cycle) is an essential metabolic pathway and plays an important role in lifespan regulation. Supplementation of α-ketoglutarate, a metabolite converted by () in the TCA cycle, increases lifespan in .