The RNA-Binding Protein SAM68 regulates cardiomyocyte differentiation by enhancing Gata4 translation
Dasti, A.; Antonelli, M. C.; Segura, M. A.; Armaos, A.; Bonnin, S.; Graf, T.; Paronetto, M. P.; Tian, T. V.; Bechara, E.; Tartaglia, G. G.
Show abstract
The signal transduction and activation of RNA (STAR) family is composed of RNA-binding proteins (RBPs) that play a central role in mammalian development. Nonetheless, the functions and modes of action that STAR proteins have in lineage specification are still poorly understood. Here, we characterized the role of STAR proteins SAM68 and QUAKING (QKI) in pluripotency and differentiation by performing their depletion through CRISPR-Cas9 in mouse embryonic stem cells (mESCs). Combining RNA-sequencing, ribosome profiling and advanced computational predictions, we found that both SAM68 and QKI regulate the mESCs self-renewal and are indispensable for cardiomyocyte differentiation. At the molecular level, we discovered that SAM68 and QKI antagonistically control the expression of cardiogenic factors. Our calculations indicated that SAM68, unlike QKI, binds the cardiogenic-specific transcription factor Gata4 in a region spanning nucleotides 500 to 1000 of the mRNA corresponding to part of the 5 untranslated region and the first exon. We validated the predictions by electrophoretic mobility shift assay and RNA immunoprecipitation showing that SAM68 controls the translation of Gata4 during mESCs differentiation towards the cardiomyocyte lineage.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency 97%
- Single-cell transcriptome analysis reveals CD34 as a novel marker of human sinoatrial node pacemaker cardiomyocytes 96%
- Evolutionary Origin of Vertebrate OCT4/POU5 Functions in Supporting Pluripotency 96%
Similar papers in this journal
- LDB1 regulates gene expression and chromatin structure in pluripotency and lineage differentiation 94%
- Nuclear compression-mediated DNA damage drives ATR-dependent Lamin expression and mouse ESC differentiation 94%
- Novel function of U7 snRNA in the repression of HERV1/LTR12s and lincRNAs in human cells 94%
Similar papers in this journal
- Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells 94%
- Chemical inhibition of SUMOylation activates the FSHD locus 94%
- Pseudotime analysis reveals novel regulatory factors for multigenic onset and monogenic transition of odorant receptor expression 94%
Similar papers in this journal
Similar papers in this journal
- The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells 96%
- Serum response factor reduces gene expression noise and confers cell state stability 96%
- Bovine Formative Embryonic Stem Cell Plasticity in Embryonic and Extraembryonic Differentiation 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.