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Detection RNA targets interacting with RBM8A in AGS cells

ABSTRACT: Detection RNA targets interacting with RBM8A in AGS cells

PROVIDER: PRJNA1237698 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32763921_1.fastq.gz	Fastqsanger.gz
	SRR32763921_2.fastq.gz	Fastqsanger.gz
	SRR32763922_1.fastq.gz	Fastqsanger.gz
	SRR32763922_2.fastq.gz	Fastqsanger.gz
	SRR32763923_1.fastq.gz	Fastqsanger.gz

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Project description:Defects in blood development are a major contributor to complex congenital anomalies. Thrombocytopenia-Absent Radius (TAR) Syndrome is a rare congenital disease presenting with reduced blood platelets (megakaryocytic thrombocytopenia) and forelimb anomalies, concurrent with variable heart and kidney defects caused by hypomorphic RBM8A/Y14 gene function. RBM8A encodes a component of the ubiquitous exon junction complex involved in mRNA splicing, transport, and nonsense-mediated decay. How perturbing a general mRNA-processing factor causes the distinct phenotypes of TAR Syndrome remains unknown. Here, we connect zebrafish rbm8a perturbation to early hematopoiesis defects via attenuated planar cell polarity (PCP) signaling involved in controlling developmental cell arrangements. Combining different genetic means to reduce rbm8a function, we find a significant reduction of cd41-positive thrombocytes in hypomorphic rbm8a larvae. Transcriptomics analysis documents rbm8a-mutant zebrafish embryos already after gastrulation accumulate mRNAs with erroneously included introns, a hallmark of defective nonsense-mediated decay. Affected mRNAs include transcripts encoding components of the non-canonical Wnt pathway involved in PCP signaling, and rbm8a mutant-embryos show hallmarks of Wnt/PCP-dependent, early convergent extension defects. We establish that reduced rbm8a function synergizes with perturbations in Wnt/PCP pathway genes including wnt5b, wnt11f2, fzd7a, and vangl2. Following axis formation, rbm8a perturbation impairs the migration and architecture of the lateral plate mesoderm (LPM) that forms the hematopoietic, cardiovascular, kidney, and forelimb skeleton progenitors. Subsequently, rbm8a perturbation impairs expression of early hematopoietic/endothelial genes including runx1a, kdrl, sox7, and the megakaryocyte regulator gfi1aa. Lastly, we document similar hematopoietic defects upon loss of vangl2. Together, our data link reduced rbm8a function to LPM migration and hematopoietic defects via attenuated Wnt/PCP signaling. Our findings establish a developmental framework that connects the complex TAR Syndrome phenotypes to a potential LPM origin.

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Detection RNA targets interacting with RBM8A in AGS cells

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