An Inorganic Biopolymer Polyphosphate Controls Positively Charged Protein Phase Transitions.

Polyphosphate (PolyP) is one of the most compact inorganic polyanionic biopolymers that participates in various physiological processes. However, the mechanism of the interaction between polyP and proteins remains poorly understood. Herein, we report that polyP can interact with positively charged green fluorescent protein, +36GFP, resulting in liquid-liquid phase separation (LLPS) by intermolecular electrostatic interactions in cells. Upon nutrient deprivation, genetically engineered Citrobacter freundii accumulates intracellular polyP at a rate of 210 µm min-1 , resulting in the compartmentation of +36GFP at the cell poles within 1 h. Medium chain-length polyP (60-mer) could induce the formation of +36GFP coacervates in vitro at a protein concentration as low as 200 nm, which is of the same magnitude as native proteins. In contrast, shorter polyP (14-mer) could not induce LLPS under the same conditions. This may offer a general approach to manipulate protein-protein interactions through LLPS.

Gain of Metabolic Benefit with Ablation of miR-149-3p from Subcutaneous Adipose Tissue in Diet-Induced Obese Mice.

The global rise in obesity has become a public health crisis. During the onset of obesity, disrupted catecholamine signals have been described to contribute to excess fat accumulation, however, the molecular and metabolic change of subcutaneous adipose tissue (SAT) upon chronic high-fat feeding has rarely been investigated. Here, we show that chronic high-fat feeding caused a significant decrease in the expression of thermogenic genes and acquisition of partial deleterious features of visceral fat in SAT. Upregulated miR-149-3p was involved in this obesity-induced "visceralization" of SAT via inhibiting PRDM16, a master regulator that promoted SAT thermogenesis. Reduction of miR-149-3p significantly increased PRDM16 expression in SAT, with improved whole-body insulin sensitivity, decreased SAT inflammation, and liver steatosis in high-fat fed mice. These findings provided direct evidence of the anti-obese and anti-diabetic effect of PRDM16 in the obese background for the first time and identified that miR-149-3p could serve as a therapeutic target to protect against diet-induced obesity and metabolic dysfunctions.