Hnrnpk is essential for embryonic limb bud development as a transcription activator and a collaborator of insulator protein Ctcf

Chen, Yuyu; Zhou, Taifeng; Liao, Zhiheng; Gao, Wenjie; Wu, Jinna; Zhang, Shun; Li, Yongyong; Liu, Hengyu; Zhou, Hang; Xu, Caixia; Su, Peiqiang

doi:10.1038/s41418-023-01207-z

Cited by 2 publications

(1 citation statement)

References 85 publications

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“…Among these family members, hnRNPK is a multifunctional protein consisting three K-homology domains (KH1, KH2, and KH3), a K-protein interactive region (KI), an N-terminal bipartite nuclear localization signal (NLS), and a nuclear shuttling domain (KNS). It demonstrates a strong a nity for single or double-stranded DNA/RNA and a wide range of proteins, which has generated growing public interest due to its crucial role in animal development and disease pathogenesis [21][22][23][24][25] . In recent times, hnRNPK has attracted signi cant attention for its involvement in regulation of cell proliferation and differentiation in different tissues [26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

HnRNPK is essential for Sertoli cells development and male fertility in mice

Zheng,

Cheng,

Bai

et al. 2023

Preprint

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Background: Sertoli cells (SCs), a type of somatic supporting cells situated within the spermatogenic niche, play a crucial role in the maturation of germ cells. Nevertheless, the precise mechanisms governing the development of SCs and their impact on spermatogenesis remain incompletely understood. Results: In this study, we have identified hnRNPK, a multifunctional protein involved in signal transduction and gene expression regulation, as a significant novel regulatory factor in the development of neonatal SCs and pre-pubertal testicular growth in mice. In order to gain a deeper understanding of the roles played by hnRNPK in spermatogenesis, we conducted a thorough investigation utilizing SCs specific Hnrnpk knockout mice, which were obtained through the crossing of Hnrnpkflox/flox mice with Amh-Cre mice. The findings demonstrated that the absence of Hnrnpk in SCs had a significant impact on various aspects, including the proliferation and localization of SCs, the organization of seminiferous tubules, the occurrence of apoptotic cell death in both SCs and germ cells within the tubules, as well as the reduction in testis size and overall fecundity. Through the integration of RNA-seq and bioinformatics analysis, our study has unveiled the dysregulation of the transcriptome-wide expression of crucial genes involved in the control of SCs and germ cells fate. These genes encompass various processes, including cell-cell adhesion, cell proliferation and migration, piRNA processing, SC differentiation, and secretion. Conclusions: Our findings highlight the indispensable role of hnRNPK in SCs for the development of the testis and also shed light on a previously unknown function of hnRNPK in male germ cell survival and differentiation, specifically by modulating cell-cell communication.

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Section: Introductionmentioning

confidence: 99%

HnRNPK is essential for Sertoli cells development and male fertility in mice

Zheng,

Cheng,

Bai

et al. 2023

Preprint

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SOX2 interacts with hnRNPK to modulate alternative splicing in mouse embryonic stem cells

Huang,

Liu,

et al. 2024

Cell Biosci

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Background SOX2 is a determinant transcription factor that governs the balance between stemness and differentiation by influencing transcription and splicing programs. The role of SOX2 is intricately shaped by its interactions with specific partners. In the interactome of SOX2 in mouse embryonic stem cells (mESCs), there is a cohort of heterogeneous nuclear ribonucleoproteins (hnRNPs) that contributes to multiple facets of gene expression regulation. However, the cross-talk between hnRNPs and SOX2 in gene expression regulation remains unclear. Results Here we demonstrate the indispensable role of the co-existence of SOX2 and heterogeneous nuclear ribonucleoprotein K (hnRNPK) in the maintenance of pluripotency in mESCs. While hnRNPK directly interacts with the SOX2-HMG DNA-binding domain and induces the collapse of the transcriptional repressor 7SK small nuclear ribonucleoprotein (7SK snRNP), hnRNPK does not influence SOX2-mediated transcription, either by modulating the interaction between SOX2 and its target cis-regulatory elements or by facilitating transcription elongation as indicated by the RNA-seq analysis. Notably, hnRNPK enhances the interaction of SOX2 with target pre-mRNAs and collaborates with SOX2 in regulating the alternative splicing of a subset of pluripotency genes. Conclusions These data reveal that SOX2 and hnRNPK have a direct protein-protein interaction, and shed light on the molecular mechanisms by which hnRNPK collaborates with SOX2 in alternative splicing in mESCs.

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Hnrnpk is essential for embryonic limb bud development as a transcription activator and a collaborator of insulator protein Ctcf

Cited by 2 publications

References 85 publications

HnRNPK is essential for Sertoli cells development and male fertility in mice

HnRNPK is essential for Sertoli cells development and male fertility in mice

SOX2 interacts with hnRNPK to modulate alternative splicing in mouse embryonic stem cells

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