Targeting redox-sensitive MBD2-NuRD condensate in cancer cells.

Transcriptional silencing of hypermethylated tumour suppressor genes is a hallmark of tumorigenesis but the underlying mechanism remains enigmatic. Here we show that methyl-CpG-binding domain protein 2 (MBD2) forms nuclear condensate in diverse cancer cells, where it assembles and navigates the chromatin remodeller NuRD complex to these gene loci for transcriptional suppression, thus fuelling tumour growth. Disturbance of MBD2 condensate reduces the level of NuRD complex-specific proteins, destabilizes heterochromatin foci, facilitates chromatin relaxation and consequently impedes tumour progression.

Excessive STAU1 condensate drives mTOR translation and autophagy dysfunction in neurodegeneration.

The double-stranded RNA-binding protein Staufen1 (STAU1) regulates a variety of physiological and pathological events via mediating RNA metabolism. STAU1 overabundance was observed in tissues from mouse models and fibroblasts from patients with neurodegenerative diseases, accompanied by enhanced mTOR signaling and impaired autophagic flux, while the underlying mechanism remains elusive. Here, we find that endogenous STAU1 forms dynamic cytoplasmic condensate in normal and tumor cell lines, as well as in mouse Huntington's disease knockin striatal cells.

A paternal protein facilitates sperm RNA delivery to regulate zygotic development.

Sperm contributes essential paternal factors, including the paternal genome, centrosome, and oocyte-activation signals, to sexual reproduction. However, it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development. Here, we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs localize.

Overexpression of GLP-1 receptors suppresses proliferation and cytokine release by airway smooth muscle cells of patients with chronic obstructive pulmonary disease via activation of ABCA1.

Glucagon-like peptide-1 (GLP‑1) is an important insulin secretagogue that possesses anti‑inflammatory effects. GLP‑1 receptor (GLP‑1R) agonists have been demonstrated to serve a pivotal role in the treatment of obstructive lung diseases, including chronic obstructive pulmonary disease (COPD). However, the specific function and underlying mechanisms of GLP‑1R in COPD remain uncertain.