A myosin for RNA Pol II

A myosin for RNA Pol II T ranscription gets a boost from myosin VI, according to fi ndings from Sarah Vreugde (DIBIT Scientifi c Institute, Milano, Italy) and colleagues. The motor might drag genes into transcription neighborhoods. While trying to understand the function of myosin VI, Vreugde noticed that its localization pattern looked much like that of RNA polymerase II. The authors then showed an association between the motor and polymerase that depends on ongoing transcription. By cross-linking myosin VI to chromatin, the group identifi ed several genes at which the motor is found. The mRNA levels of these genes decreased when myosin VI levels were reduced. Vreugde next hopes to inhibit just the nuclear pool of myosin VI and then do genome-wide analyses to identify more affected genes. Assuming its infl uence is widespread, the motor might spool the DNA past aggregates of RNA polymerases or recruit stretches of DNA to transcription factories. “DNA recruitment to transcription factories would be heavy work,” says Vreugde. “But myosin is well-suited to accomplish that.” Whether its unusual preference to move toward actin minus ends helps myosin VI at all is unclear, as the polarity of the nuclear actin network is not known and probably dynamic. The only other known nuclear myosin, myosin I, is plus-end directed but still enhances transcription by all the RNA polymerases. Reference: Vreugde, S., et al. 2006. Mol. Cell. 23:749–755. T cells told to keep rolling A T cell coreceptor keeps T cells moving so that they are not overactivated, according to Helga Schneider, Christopher Rudd (University of Cambridge, UK), and colleagues. By not lingering too long, killer T cells might be at their most effi cient. Rudd’s group recently found that this coreceptor, called CTLA-4, was needed for integrin activation. Integrins go hand-in-hand with cell migration, which the authors now show is increased by CTLA-4 engagement. When T cells meet the right antigen-presenting cell (APC), they normally stop and interact with the APC to get activated. This stopping phase, the authors show, is limited by CTLA-4, which is found on all activated T cells and binds to ligands on the APC. By restricting the interaction time, CTLA-4 may prevent responses to low-affi nity self-antigens that cause autoimmunity. This idea is supported by the severe autoimmunity found in mice lacking CTLA-4. Rudd suspects that their T cells “park next to an APC for so long that they start accumulating signals against self-antigens.” The anti–stop signal might have been designed to make cytotoxic T cells more effi cient in killing infected or cancerous cells. It might also explain why anti–CTLA-4 antibodies succeed as cancer therapies, if they act as ligand mimics. “The release of [cytotoxic] granzymes is relatively quick,” says Rudd. “The T cell can kill the tumor target cell and not stick around any longer than it needs to, take off again and encounter another target.” Reference: Schneider, H., et al. 2006. Science. doi:10.1126/science.1131078.