Drosophila Imp iCLIP identifies an RNA assemblage coordinating F-actin formation.

Background: Post-transcriptional RNA regulons ensure coordinated expression of monocistronic mRNAs encoding functionally related proteins. In this study, we employ a combination of RIP-seq and short- and long-wave individual-nucleotide resolution crosslinking and immunoprecipitation (iCLIP) technologies in Drosophila cells to identify transcripts associated with cytoplasmic ribonucleoproteins (RNPs) containing the RNA-binding protein Imp.

Results: We find extensive binding of Imp to 3' UTRs of transcripts that are involved in F-actin formation.

Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties.

The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy-Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an aqueous buffer and both phospholipids are hydrolyzed by phospholipase A(2), but with different conversion rates and extent of hydrolysis. The cytotoxicity was evaluated in HT-29 and Colo205 cells and the conjugates induced cell death in the presence of phospholipase A(2) and surprisingly also in the absence of the enzyme.

Liposomal formulation of retinoids designed for enzyme triggered release.

The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm.

Embryonic expression of Drosophila IMP in the developing CNS and PNS.

Drosophila IMP (dIMP) is related to the vertebrate RNA-binding proteins IMP1-3, ZBP1, Vg1RBP and CRD-BP, which are involved in RNA regulatory processes such as translational repression, localization and stabilization. The proteins are expressed in many fetal tissues, including the developing nervous system, and IMP up-regulation in solid tumors correlates with a high metastatic potential and poor prognosis. In this study, we used immunohistochemistry and live-imaging of an endogenous promoter-driven GFP-dIMP fusion protein to reveal the expression pattern of dIMP protein throughout embryogenesis.

Nuclear transit of human zipcode-binding protein IMP1.

The human IMPs (insulin-like growth factor II mRNA-binding proteins) belong to a vertebrate zipcode-binding protein family consisting of two RNA recognition motifs and four K homology domains and have been implicated in cytoplasmic mRNA localization, turnover and translational control. In the present study, we show that IMP1 is capable of translocating into nuclei of NIH 3T3 fibroblasts and its immunoreactivity is present in the nuclei of human spermatogenic cells. IMP1 does not contain a simple import signal, but nuclear entry was facilitated by disruption of RNA binding and cytoplasmic granule formation.