A mechanical perspective on phagocytic cup formation.

Phagocytosis is a widespread and evolutionarily conserved process with diverse biological functions, ranging from engulfment of invading microbes during infection to clearance of apoptotic debris in tissue homeostasis. Along with differences in biochemical composition, phagocytic targets greatly differ in physical attributes, such as size, shape, and rigidity, which are now recognized as important regulators of this process. Force exertion at the cell-target interface and cellular mechanical changes during phagocytosis are emerging as crucial factors underlying sensing of such target properties. With technological developments, mechanical aspects of phagocytosis are increasingly accessible experimentally, revealing remarkable organizational complexity of force exertion. An increasingly high-resolution picture is emerging of how target physical cues and cellular mechanical properties jointly govern important steps throughout phagocytic engulfment.

KDM5 lysine demethylases are involved in maintenance of 3'UTR length.

The complexity by which cells regulate gene and protein expression is multifaceted and intricate. Regulation of 3' untranslated region (UTR) processing of mRNA has been shown to play a critical role in development and disease. However, the process by which cells select alternative mRNA forms is not well understood. We discovered that the Saccharomyces cerevisiae lysine demethylase, Jhd2 (also known as KDM5), recruits 3'UTR processing machinery and promotes alteration of 3'UTR length for some genes in a demethylase-dependent manner. Interaction of Jhd2 with both chromatin and RNA suggests that Jhd2 affects selection of polyadenylation sites through a transcription-coupled mechanism. Furthermore, its mammalian homolog KDM5B (also known as JARID1B or PLU1), but not KDM5A (also known as JARID1A or RBP2), promotes shortening of CCND1 transcript in breast cancer cells. Consistent with these results, KDM5B expression correlates with shortened CCND1 in human breast tumor tissues. In contrast, both KDM5A and KDM5B are involved in the lengthening of DICER1. Our findings suggest both a novel role for this family of demethylases and a novel targetable mechanism for 3'UTR processing.