Widespread transcript shortening through alternative polyadenylation in secretory cell differentiation.

Most eukaryotic genes produce alternative polyadenylation (APA) isoforms. Here we report that, unlike previously characterized cell lineages, differentiation of syncytiotrophoblast (SCT), a cell type critical for hormone production and secretion during pregnancy, elicits widespread transcript shortening through APA in 3'UTRs and in introns. This global APA change is observed in multiple in vitro trophoblast differentiation models, and in single cells from placentas at different stages of pregnancy.

Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells (NPCs).

Human brain development proceeds through a series of precisely orchestrated processes, with earlier stages distinguished by proliferation, migration, and neurite outgrowth; and later stages characterized by axon/dendrite outgrowth and synapse formation. In neurodevelopmental disorders, often one or more of these processes are disrupted, leading to abnormalities in brain formation and function. With the advent of human induced pluripotent stem cell (hiPSC) technology, researchers now have an abundant supply of human cells that can be differentiated into virtually any cell type, including neurons.

Promyelocytic leukemia nuclear bodies support a late step in DNA double-strand break repair by homologous recombination.

The PML protein and PML nuclear bodies (PML-NB) are implicated in multiple cellular functions relevant to tumor suppression, including DNA damage response. In most cases of acute promyelocytic leukemia, the PML and retinoic acid receptor alpha (RARA) genes are translocated, resulting in expression of oncogenic PML-RARα fusion proteins. PML-NB fail to form normally, and promyelocytes remain in an undifferentiated, abnormally proliferative state.

Daxx contains two nuclear localization signals and interacts with importin alpha3.

Daxx plays a major role in several important signaling pathways including transcription and cell death. It has been postulated that Daxx regulates both events from the nucleus; however, the mechanism by which Daxx is localized in the nucleus remains obscure. Here we show that nuclear localization of Daxx is controlled by two independent signals and importin 3.

Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin alpha3.

The nuclear receptor coactivator RAC3 (also known as SRC-3/ACTR/AIB1/p/CIP/TRAM-1) belongs to the p160 coactivator family, which are involved in several physiological processes and diseases. Here we have investigated how RAC3 is translocated into the nucleus and show that it is mediated through a bipartite NLS and importin alpha3. This bipartite NLS is located within the conserved bHLH domain, and its mutation abolished nuclear localization.

Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators.

Members of the p160 nuclear receptor coactivators interact with liganded nuclear receptors to enhance transcription of target genes. Here we identify a novel family of ankyrin repeats containing cofactors (ANCOs) that interact with the p160 coactivators. ANCO-1 binds to the conserved Per-Arnt-Sim (PAS) region of the p160 coactivators.