Interaction Between Sympk and Oct4 Promotes Mouse Embryonic Stem Cell Proliferation

Yu, Jianping; Lu, Weisi; Ge, Tianyu; Huang, Rui; Chen, Bohong; Ye, Miaoman; Bai, Yinshan; Shi, Guang; Songyang, Zhou; Ma, Wenbin; Huang, Junjiu

doi:10.1002/stem.2992

Cited by 3 publications

(3 citation statements)

References 40 publications

(56 reference statements)

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“…We also cannot rule out that an increase in levels of some subunits of the complex may be associated with other roles in the cell besides mRNA 3’ end processing. For example, the symplekin subunit of CPSF also functions at the surface of the cell in tight junctions ( 89 ) and its interaction with Oct4 promotes the activity of this transcriptional driver of cell stemness ( 90 ). Thus, subcomplexes can exist within the cell, suggesting the intriguing possibility that this could be another point at which polyadenylation capacity of the cell could be regulated.…”

Section: Discussionmentioning

confidence: 99%

Macrophage differentiation is marked by increased abundance of the mRNA 3’ end processing machinery, altered poly(A) site usage, and sensitivity to the level of CstF64

2023

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Regulation of mRNA polyadenylation is important for response to external signals and differentiation in several cell types, and results in mRNA isoforms that vary in the amount of coding sequence or 3’ UTR regulatory elements. However, its role in differentiation of monocytes to macrophages has not been investigated. Macrophages are key effectors of the innate immune system that help control infection and promote tissue-repair. However, overactivity of macrophages contributes to pathogenesis of many diseases. In this study, we show that macrophage differentiation is characterized by shortening and lengthening of mRNAs in relevant cellular pathways. The cleavage/polyadenylation (C/P) proteins increase during differentiation, suggesting a possible mechanism for the observed changes in poly(A) site usage. This was surprising since higher C/P protein levels correlate with higher proliferation rates in other systems, but monocytes stop dividing after induction of differentiation. Depletion of CstF64, a C/P protein and known regulator of polyadenylation efficiency, delayed macrophage marker expression, cell cycle exit, attachment, and acquisition of structural complexity, and impeded shortening of mRNAs with functions relevant to macrophage biology. Conversely, CstF64 overexpression increased use of promoter-proximal poly(A) sites and caused the appearance of differentiated phenotypes in the absence of induction. Our findings indicate that regulation of polyadenylation plays an important role in macrophage differentiation.

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Section: Discussionmentioning

confidence: 99%

Macrophage differentiation is marked by increased abundance of the mRNA 3’ end processing machinery, altered poly(A) site usage, and sensitivity to the level of CstF64

2023

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“…Importantly, SYMPK has been identified as a cofactor of RBFOX2 and NOVA2 to regulate alternative mRNA splicing ( Misra et al, 2015 ). Recently, it has been reported that SYMPK promotes the self-renewal and pluripotency of embryonic stem cells (ESCs) through interaction with OCT4 ( Yu et al, 2019 ). Nevertheless, the function of SYMPK in male germ cells is still unclear.…”

Section: Introductionmentioning

confidence: 99%

SYMPK Is Required for Meiosis and Involved in Alternative Splicing in Male Germ Cells

Zhan

Zheng

et al. 2021

Front. Cell Dev. Biol.

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SYMPK is a scaffold protein that supports polyadenylation machinery assembly on nascent transcripts and is also involved in alternative splicing in some mammalian somatic cells. However, the role of SYMPK in germ cells remains unknown. Here, we report that SYMPK is highly expressed in male germ cells, and germ cell-specific knockout (cKO) of Sympk in mouse leads to male infertility. Sympk cKODdx4–cre mice showed reduced spermatogonia at P4 and almost no germ cells at P18. Sympk cKOStra8–Cre spermatocytes exhibit defects in homologous chromosome synapsis, DNA double-strand break (DSB) repair, and meiotic recombination. RNA-Seq analyses reveal that SYMPK is associated with alternative splicing, besides regulating the expressions of many genes in spermatogenic cells. Importantly, Sympk deletion results in abnormal alternative splicing and a decreased expression of Sun1. Taken together, our results demonstrate that SYMPK is pivotal for meiotic progression by regulating pre-mRNA alternative splicing in male germ cells.

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“…Midbodies form during final stages of cytokinesis and are rich in microtubules that are stabilized by KIF20B (Janisch et al, 2018). In ESCs KIF20B expression levels are tightly regulated by Symplekin, which together with Oct4 control stem cell pluripotency expression profiles (Yu et al, 2019). Kif20b knockdown disrupts cellular polarization and cells display cytokinetic defects leading to the accumulation of apoptotic multinucleated cells (Georges et al, 2019).…”

Section: Kif20bmentioning

confidence: 99%

The role of SRSF3 in nuclear splicing surveillance

Wegener¹

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Funktionsverlustmutante von Zc3h14 die Zellzyklus-Regulation beeinträchtigen und das neuronale Expressionsprofil stören. Patienten, die an dem Fragilen-X-Syndrom oder einer Septin 7 assoziierten Alzheimer-Erkrankung leiden, weisen die gleichen Krankheitssymptome auf wie Patienten, die eine mutierte Zc3h14-Isoform exprimieren. Unsere Ergebnisse zeigen, dass der Export von Fmr1 und Sept7 über Zc3h14 vermittelt wird. Daher könnte das Krankheitsbild, das durch den Verlust der physiologischen synaptischen Plastizität charakterisiert ist, auf eine Beeinträchtigung des Exports von Fmr1 und Sept7 zurückzuführen sein. Obwohl wir aktuell nicht wissen, ob diese Krankheiten mit unserem vorgeschlagenen Exportmodell in Verbindung stehen, könnten zukünftige Versuche und experimentelle Ansätze in differenzierten P19-Zellen Einblicke in das neuronale Exportsystem und in die Pathogenese multipler neuronaler Entwicklungsstörungen gewähren.Recent developments combining quantitative transcriptomics and proteomics led to the identification of numerous RBPs, its co-factors and RNA targets and unveiled a vast amount of interactions and regulatory networks that are connected with every process of the mRNA lifecycle. Studies combining in vivo UV RNAprotein crosslinking followed by polyA-RNA pulldown and protein mass spectrometry (RNA Interactome Capture) revealed that nearly 50% of these networks affected RBPs that act in RNA metabolic pathways, such as splicing, 3'end processing, polyadenylation, and mRNA transport (Gerstberger et al., 2014).RBPs can act synergistically and enhance each other's RNA binding affinity and specificity (see Figure 2 on the left). In contrast to this cooperative interplay, other RBPs act antagonistically and compete for RNA binding sites to exert their functions (Dassi, 2017). In addition, multiple RBPs regulate each other's expression in a mutual interplay and fine-tune their abundance and action by controlling their protein expression (Dassi, 2017). Since the RBP network is interlinked between mRNA processes, the composition and balance of competing and cooperating RBPs on the target RNA species defines the regulatory outcome and makes RBPs the major players in post-transcriptional regulation. promotes the first catalytical splicing reaction and generates complex C, which contains a free exon and the intronexon lariat intermediate. After several rearrangements, the second catalytic step occurs, resulting in a postspliceosome complex that contains the lariat intron and spliced exons. U2, U5 and U6 are finally released from the post-splicing mRNPs and recycled. C) U1 and U2 bind to the 5'ss and the branch point at the 3'ss respectively to form complex E. Complex A formation involves the association of U4-U6, leading to the base pairing of U6 with U2, and U5 with exonic sequences near the 5'ss. An extensive network of base-pairing interactions is formed between U6 and U2, juxtaposing the 5ʹss and branch-point adenosine for the first catalytic step of splicing (mod. (Matera & Wang, 2014)).named with the prefix S...

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Interaction Between Sympk and Oct4 Promotes Mouse Embryonic Stem Cell Proliferation

Cited by 3 publications

References 40 publications

Macrophage differentiation is marked by increased abundance of the mRNA 3’ end processing machinery, altered poly(A) site usage, and sensitivity to the level of CstF64

Macrophage differentiation is marked by increased abundance of the mRNA 3’ end processing machinery, altered poly(A) site usage, and sensitivity to the level of CstF64

SYMPK Is Required for Meiosis and Involved in Alternative Splicing in Male Germ Cells

The role of SRSF3 in nuclear splicing surveillance

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