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Literature DB >> 29866654

Poly(C)-Binding Protein Pcbp2 Enables Differentiation of Definitive Erythropoiesis by Directing Functional Splicing of the Runx1 Transcript.

Louis R Ghanem^1,2,3, Andrew Kromer³, Ian M Silverman³, Xinjun Ji³, Matthew Gazzara³, Nhu Nguyen³, Gabrielle Aguilar⁴, Massimo Martinelli^4,5, Yoseph Barash³, Stephen A Liebhaber^6,7.

Abstract

Formation of the mammalian hematopoietic system is under a complex set of developmental controls. Here, we report that mouse embryos lacking the KH domain poly(C) binding protein, Pcbp2, are selectively deficient in the definitive erythroid lineage. Compared to wild-type controls, transcript splicing analysis of the Pcbp2-/- embryonic liver reveals accentuated exclusion of an exon (exon 6) that encodes a highly conserved transcriptional control segment of the hematopoietic master regulator, Runx1. Embryos rendered homozygous for a Runx1 locus lacking this cassette exon (Runx1ΔE6) effectively phenocopy the loss of the definitive erythroid lineage in Pcbp2-/- embryos. These data support a model in which enhancement of Runx1 cassette exon 6 inclusion by Pcbp2 serves a critical role in development of hematopoietic progenitors and constitutes a critical step in the developmental pathway of the definitive erythropoietic lineage.

Entities: Chemical Gene Species

Keywords: Pcbp2; RNA processing; Runx1; alternative splicing; definitive erythropoiesis; erythropoiesis; hematopoiesis; myeloid stem cells; posttranscriptional control mechanisms; primitive erythropoiesis

Mesh：

Substances：

Year: 2018 PMID： 29866654 PMCID： PMC6066754 DOI： 10.1128/MCB.00175-18

Source DB: PubMed Journal: Mol Cell Biol ISSN： 0270-7306 Impact factor: 4.272

84 in total

1. A novel set of nuclear localization signals determine distributions of the alphaCP RNA-binding proteins.

Authors: Alexander N Chkheidze; Stephen A Liebhaber
Journal: Mol Cell Biol Date: 2003-12 Impact factor: 4.272

2. Alternative Runx1 promoter usage in mouse developmental hematopoiesis.

Authors: Thomas Bee; Kate Liddiard; Gemma Swiers; Sorrel R B Bickley; Chris S Vink; Andrew Jarratt; Jim R Hughes; Alexander Medvinsky; Marella F T R de Bruijn
Journal: Blood Cells Mol Dis Date: 2009-05-21 Impact factor: 3.039

3. A set of highly conserved RNA-binding proteins, alphaCP-1 and alphaCP-2, implicated in mRNA stabilization, are coexpressed from an intronless gene and its intron-containing paralog.

Authors: A V Makeyev; A N Chkheidze; S A Liebhaber
Journal: J Biol Chem Date: 1999-08-27 Impact factor: 5.157

4. The 3' untranslated region complex involved in stabilization of human alpha-globin mRNA assembles in the nucleus and serves an independent role as a splice enhancer.

Authors: Xinjun Ji; Jian Kong; Russ P Carstens; Stephen A Liebhaber
Journal: Mol Cell Biol Date: 2007-02-26 Impact factor: 4.272

5. AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis.

Authors: Motoshi Ichikawa; Takashi Asai; Toshiki Saito; Sachiko Seo; Ieharu Yamazaki; Tetsuya Yamagata; Kinuko Mitani; Shigeru Chiba; Seishi Ogawa; Mineo Kurokawa; Hisamaru Hirai
Journal: Nat Med Date: 2004-02-15 Impact factor: 53.440

6. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis.

Authors: T Okuda; J van Deursen; S W Hiebert; G Grosveld; J R Downing
Journal: Cell Date: 1996-01-26 Impact factor: 41.582

4. Knockdown of Splicing Complex Protein PCBP2 Reduces Extravillous Trophoblast Differentiation Through Transcript Switching.

Authors: Danai Georgiadou; Souad Boussata; Remco Keijser; Dianta A M Janssen; Gijs B Afink; Marie van Dijk
Journal: Front Cell Dev Biol Date: 2021-05-20

4 in total

Poly(C)-Binding Protein Pcbp2 Enables Differentiation of Definitive Erythropoiesis by Directing Functional Splicing of the Runx1 Transcript.

1. A novel set of nuclear localization signals determine distributions of the alphaCP RNA-binding proteins.

2. Alternative Runx1 promoter usage in mouse developmental hematopoiesis.

3. A set of highly conserved RNA-binding proteins, alphaCP-1 and alphaCP-2, implicated in mRNA stabilization, are coexpressed from an intronless gene and its intron-containing paralog.

4. The 3' untranslated region complex involved in stabilization of human alpha-globin mRNA assembles in the nucleus and serves an independent role as a splice enhancer.

5. AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis.

6. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis.

7. Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A.

8. Runx1 downregulates stem cell and megakaryocytic transcription programs that support niche interactions.

9. Control of alternative splicing by forskolin through hnRNP K during neuronal differentiation.

Review 10. Primitive and definitive erythropoiesis in mammals.

Review 1. Picornaviruses and RNA Metabolism: Local and Global Effects of Infection.

2. Systematic profiling of a novel prognostic alternative splicing signature in hepatocellular carcinoma.

3. RNA-Binding Proteins PCBP1 and PCBP2 Are Critical Determinants of Murine Erythropoiesis.

4. Knockdown of Splicing Complex Protein PCBP2 Reduces Extravillous Trophoblast Differentiation Through Transcript Switching.