PPS, a Large Multidomain Protein, Functions with Sex-Lethal to Regulate Alternative Splicing in Drosophila

Alternative splicing controls the expression of many genes, including the Drosophila sex determination gene Sex-lethal (Sxl). Sxl expression is controlled via a negative regulatory mechanism where inclusion of the translation-terminating male exon is blocked in females. Previous studies have shown that the mechanism leading to exon skipping is autoregulatory and requires the SXL protein to antagonize exon inclusion by interacting with core spliceosomal proteins, including the U1 snRNP protein Sans-fille (SNF). In studies begun by screening for proteins that interact with SNF, we identified PPS, a previously uncharacterized protein, as a novel component of the machinery required for Sxl male exon skipping. PPS encodes a large protein with four signature motifs, PHD, BRK, TFS2M, and SPOC, typically found in proteins involved in transcription. We demonstrate that PPS has a direct role in Sxl male exon skipping by showing first that loss of function mutations have phenotypes indicative of Sxl misregulation and second that the PPS protein forms a complex with SXL and the unspliced Sxl RNA. In addition, we mapped the recruitment of PPS, SXL, and SNF along the Sxl gene using chromatin immunoprecipitation (ChIP), which revealed that, like many other splicing factors, these proteins bind their RNA targets while in close proximity to the DNA. Interestingly, while SNF and SXL are specifically recruited to their predicted binding sites, PPS has a distinct pattern of accumulation along the Sxl gene, associating with a region that includes, but is not limited to, the SxlPm promoter. Together, these data indicate that PPS is different from other splicing factors involved in male-exon skipping and suggest, for the first time, a functional link between transcription and SXL–mediated alternative splicing. Loss of zygotic PPS function, however, is lethal to both sexes, indicating that its role may be of broad significance

MODELING AND CONTROL OF A SNAKE-LIKE SERIAL-LINK STRUCTURE

ture (Under the direction of Kazufumi Ito). The topic considered is the modeling and control of a snake-like serial-link struc-ture. The system is assumed to have torque controls about the joints, is considered to lie in an isotropic plane, and is assumed to interact with this plane in a manner which adheres to some suitable friction laws. Such a structure is hyper-redundant, making the robotic realization thereof potentially robust with regards to mechanical failure and highly suited for obstacle avoidance tasks and terrain adaptability. It is for these reasons that the structure is studied. Lagrangian mechanics is used to develop a mathematical model for the system. The resulting dynamics possess symmetries which allow them to be placed in a reduced form. Using this form in conjunction with a technique known as feedback linearization, one finds that the dynamics are driven by a three state system describing the evolution of generalized momenta with respect to the device’s internal shape progression. The problem is to determine whether or not there is a shape trajectory that can elicit bulk structure movement. In order to determine the appropriate shape for this task a two-pronged approach is taken. One approach is to make a shape selection based on the principle mechanism of undulatory locomotion. The other approach is to set up a variational problem to determine an optimal locomotive shape