Generation of an induced pluripotent stem cell line from a patient with epileptic encephalopathy caused by the CYFIP2 R87C variant.

Induced pluripotent stem cells (iPSCs) opened the possibility to use patient cells as a model for several diseases. iPSCs can be reprogrammed from somatic cells collected in a non-invasive way, and then differentiated into any other cell type, while maintaining the donor´s genetic background. CYFIP2 variants were associated with the onset of an early form of epileptic encephalopathy. Studies with patients showed that the R87C variant seems to be one of the variants that causes more severe disease, however, to date there are no studies with a human cell model that allows investigation of the neuronal phenotype of the R87C variant. Here, we generated an iPSC line from a patient with epileptic encephalopathy caused by the CYFIP2 R87C variant. We obtained iPSC clones by reprogramming urinary progenitor cells from a female patient. The generated iPSC line presented a pluripotent stem cell morphology, normal karyotype, expressed pluripotency markers and could be differentiated into the three germ layers. In further studies, this cell line could be used as model for epileptic encephalopathy disease and drug screening studies.

Modulation and function of Pumilio proteins in cancer.

Post-transcriptional regulation is involved in tumorigenesis, and in this control, RNA-binding proteins are the main protagonists. Pumilio proteins are highly conserved RNA-binding proteins that regulate many aspects of RNA processing. The dysregulation of Pumilio expression is associated with different types of cancer. This review summarizes the roles of Pumilio 1 and Pumilio 2 in cancer and discusses the factors that account for their distinct biological functions. Pumilio levels seem to be related to tumor progression and poor prognoses in some kinds of tumors, such as lung, pancreatic, prostate, and cervical cancers. Pumilio 1 is associated with cancer proliferation, migration, and invasion, and so is Pumilio 2, although there are contradictory reports regarding the latter. Furthermore, the circular RNA, circPUM1, has been described as a miRNAs sponge, regulating miRNA involved in the cell cycle. The expression and function of Pumilio proteins depend on the fine adjustment of a set of modulators, including miRNAs, lncRNAs, and circRNAs; this demonstrates that Pumilio plays an important role in tumorigenesis through a variety of regulatory axes.

Cytoplasmic FMR1 interacting protein (CYFIP) family members and their function in neural development and disorders.

In humans, the cytoplasmic FMR1 interacting protein (CYFIP) family is composed of CYFIP1 and CYFIP2. Despite their high similarity and shared interaction with many partners, CYFIP1 and CYFIP2 act at different points in cellular processes. CYFIP1 and CYFIP2 have different expression levels in human tissues, and knockout animals die at different time points of development. CYFIP1, similar to CYFIP2, acts in the WAVE regulatory complex (WRC) and plays a role in actin dynamics through the activation of the Arp2/3 complex and in a posttranscriptional regulatory complex with the fragile X mental retardation protein (FMRP). Previous reports have shown that CYFIP1 and CYFIP2 may play roles in posttranscriptional regulation in different ways. While CYFIP1 is involved in translation initiation via the 5'UTR, CYFIP2 may regulate mRNA expression via the 3'UTR. In addition, this CYFIP protein family is involved in neural development and maturation as well as in different neural disorders, such as intellectual disabilities, autistic spectrum disorders, and Alzheimer's disease. In this review, we map diverse studies regarding the functions, regulation, and implications of CYFIP proteins in a series of molecular pathways. We also highlight mutations and their structural effects both in functional studies and in neural diseases.

Effects of PUMILIO1 and PUMILIO2 knockdown on cardiomyogenic differentiation of human embryonic stem cells culture.

Posttranscriptional regulation plays a fundamental role in the biology of embryonic stem cells (ESCs). Many studies have demonstrated that multiple mRNAs are coregulated by one or more RNA-binding proteins (RBPs) that orchestrate mRNA expression. A family of RBPs, which is known as the Pumilio-FBF (PUF) family, is highly conserved among different species and has been associated with the undifferentiated and differentiated states of different cell lines. In humans, two homologs of the PUF family have been found: Pumilio 1 (PUM1) and Pumilio 2 (PUM2). To understand the role of these proteins in human ESCs (hESCs), we first assessed the influence of the silencing of PUM1 and PUM2 on pluripotency genes and found that the knockdown of Pumilio genes significantly decreased the OCT4 and NANOG mRNA levels and reduced the amount of nuclear OCT4, which suggests that Pumilio proteins play a role in the maintenance of pluripotency in hESCs. Furthermore, we observed that PUM1-and-PUM2-silenced hESCs exhibited improved efficiency of in vitro cardiomyogenic differentiation. Through an in silico analysis, we identified mRNA targets of PUM1 and PUM2 that are expressed at the early stages of cardiomyogenesis, and further investigation will determine whether these target mRNAs are active and involved in the progression of cardiomyogenesis. Our findings contribute to the understanding of the role of Pumilio proteins in hESC maintenance and differentiation.