Aberrant splicing is typically attributed to splice-factor (SF) mutation and contributes to malignancies including acute myeloid leukemia (AML). Here, we discovered a mutation-independent means to extensively reprogram alternative splicing (AS). We showed that the dysregulated expression of eukaryotic translation initiation factor eIF4E elevated selective splice-factor production, thereby impacting multiple spliceosome complexes, including factors mutated in AML such as SF3B1 and U2AF1.
View Article and Find Full Text PDFThe translation of RNA into protein is a dynamic process which is heavily regulated during normal cell physiology and can be dysregulated in human malignancies. Its dysregulation can impact selected groups of RNAs, modifying protein levels independently of transcription. Integral to their suitability for translation, RNAs undergo a series of maturation steps including the addition of the mG cap on the 5' end of RNAs, splicing, as well as cleavage and polyadenylation (CPA).
View Article and Find Full Text PDFCell cycle is a highly regulated process that is finely coordinated by a plethora of interconnected regulators. In this paper, we report that post-transcriptional mechanisms mediated by the RNA-binding protein Staufen1 (STAU1) are essential for the proliferation of non-transformed cells (hTERT-RPE1 and IMR90). Cell sorting quantification and time-lapse video microscopy using FUCCI-hTERT-RPE1 cells identified the G/S and G/M phase transitions of the cell cycle as crucial steps for STAU1 functions.
View Article and Find Full Text PDFStaufen1 (Stau1) is a ribonucleic acid (RNA)-binding protein involved in the post-transcriptional regulation of gene expression. Recent studies indicate that Stau1-bound messenger RNAs (mRNAs) mainly code for proteins involved in transcription and cell cycle control. Consistently, we report here that Stau1 abundance fluctuates through the cell cycle in HCT116 and U2OS cells: it is high from the S phase to the onset of mitosis and rapidly decreases as cells transit through mitosis.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2014
The cellular response to highly genotoxic DNA double-strand breaks (DSBs) involves the exquisite coordination of multiple signaling and repair factors. Here, we conducted a functional RNAi screen and identified BAP1 as a deubiquitinase required for efficient assembly of the homologous recombination (HR) factors BRCA1 and RAD51 at ionizing radiation (IR) -induced foci. BAP1 is a chromatin-associated protein frequently inactivated in cancers of various tissues.
View Article and Find Full Text PDFBiochem Biophys Res Commun
July 2011
AmyTM is a truncated mutant of the α-amylase of Bacillus stearothermophilus US100. It has been derived from the wild type amylase gene via a reading frame shift, following a tandem duplication of the mutant primer, associated to an Adenine base deletion. AmyTM was composed of 720 nucleotides encoding 240 amino acid residues out of 549 of the wild type.
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