<i>Rbm14</i> maintains the integrity of genomic DNA during early mouse embryogenesis via mediating alternative splicing

Li, Jing; Wang, Chenxin; Feng, Guihai; Zhang, Linlin; Chen, Guilai; Sun, Hao; Wang, Jiaqiang; Zhang, Ying; Zhou, Qi; Li, Wei

doi:10.1111/cpr.12724

Cited by 10 publications

(7 citation statements)

References 49 publications

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“…We believe that the interaction between FOXO1 and hnRNPK may be involved in the regulation of the expression of a large group of genes and play certain roles in cancer and diabetes. RNA binding motif protein 14 (RBM14), also known as PSP2 or quasi dot protein, is an RNA binding protein belonging to the RBM (RNA binding motif) protein [ 39 ]. RBM 14 has two RNA recognition motifs (RRMs) and a prion-like domain (PLD) at the N-terminus.…”

Section: Discussionmentioning

confidence: 99%

Study of FOXO1-interacting proteins using TurboID-based proximity labeling technology

Guo

et al. 2023

BMC Genomics

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Background Protein‒protein interactions (PPIs) are the foundation of the life activities of cells. TurboID is a biotin ligase with higher catalytic efficiency than BioID or APEX that reduces the required labeling time from 18 h to 10 min. Since many proteins participate in binding and catalytic events that are very short-lived, it is theoretically possible to find relatively novel binding proteins using the TurboID technique. Cell proliferation, apoptosis, autophagy, oxidative stress and metabolic disorders underlie many diseases, and forkhead box transcription factor 1 (FOXO1) plays a key role in these physiological and pathological processes. Results The FOXO1-TurboID fusion gene was transfected into U251 astrocytes, and a cell line stably expressing FOXO1 was constructed. While constructing the FOXO1 overexpression plasmid, we also added the gene sequence of TurboID to perform biotin labeling experiments in the successfully fabricated cell line to look for FOXO1 reciprocal proteins. Label-free mass spectrometry analysis was performed, and 325 interacting proteins were found. A total of 176 proteins were identified in the FOXO1 overexpression group, and 227 proteins were identified in the Lipopolysaccharide -treated group (Lipopolysaccharide, LPS). Wild-type U251 cells were used to exclude interference from nonspecific binding. The FOXO1-interacting proteins hnRNPK and RBM14 were selected for immunoprecipitation and immunofluorescence verification. Conclusion The TurboID technique was used to select the FOXO1-interacting proteins, and after removing the proteins identified in the blank group, a large number of interacting proteins were found in both positive groups. This study lays a foundation for further study of the function of FOXO1 and the regulatory network in which it is involved.

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Section: Discussionmentioning

confidence: 99%

Study of FOXO1-interacting proteins using TurboID-based proximity labeling technology

Guo

et al. 2023

BMC Genomics

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“…Furthermore, RBM10 knockout led to a marked decrease in the proliferation of mouse embryonic stem cells and dramatically affected the size of embryoid bodies (Rodor et al, 2017 ). Similarly, RBM14 maintained genome integrity during early mouse embryogenesis and was indispensable for the pluripotency of mouse embryonic stem cells and mesoderm development (Chen et al, 2018 ; Li et al, 2020 ). In this study, we show that RBM14 is co-localized with the spindle during meiotic progression in the mouse oocytes.…”

Section: Discussionmentioning

confidence: 99%

RBM14 Modulates Tubulin Acetylation and Regulates Spindle Morphology During Meiotic Maturation in Mouse Oocytes

Qin

Yuan

et al. 2021

Front. Cell Dev. Biol.

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RBM14 is an RNA-binding protein that regulates spindle integrity in mitosis; however, its functions during meiosis are still unclear. In this study, we discovered that RBM14 expression was down-regulated in oocytes from old mice. The RBM14 distribution at different stages of meiosis was explored, while it presents overlapped localization patterns with α-tubulin in MI- and MII-stage oocytes. Treatment of MI-stage oocytes with spindle-perturbing agents revealed that RBM14 was co-localized with microtubules. RBM14 knockdown with RBM14-specific morpholino showed that RBM14-depleted oocytes underwent symmetric division compared to the controls. RBM14 knockdown also resulted in spindle defects and chromosome abnormalities during oocyte maturation, presumably due to α-tubulin hyperacetylation. Co-immunoprecipitation analysis demonstrated that RBM14 is interacted with endogenous α-tubulin in mammalian cells. These findings indicate that RBM14 is an essential modulator of oocyte meiotic maturation by regulating α-tubulin acetylation to affect spindle morphology and chromosome alignment. Consequently, RBM14 represents a potential biomarker of oocyte quality and a novel therapeutic target in women with oocyte maturation failure.

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“…RBM14 plays a role in alternative splicing, regulation of DNA repair via the canonical non-homologous end joining (c-NHEJ) pathway, and is part of the HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein (HDP-RNP) complex that regulates innate immune response through cGAS-STING signaling [45][46][47] . Its depletion leads to disrupted genome integrity and the accumulation of DNA damage during mouse embryogenesis 48 , and hinders mitotic spindle assembly and chromosome segregation in human U2OS bone osteosarcoma cells 49 .…”

Section: Rbm14 Overexpression Reduces Proliferation Of Human Lung And...mentioning

confidence: 99%

“…48 h prior sample collection. Pellets from 2 million cells were collected and lysed with RIPA lysis buffer (20 mM Tris-HCl at pH 7.5, 150 nM NaCl, 1 mM Na 2 EDTA, 1 mM EGTA, 1% NP-40, 1% sodium deoxycholate, 2.5 mM sodium pyrophosphate, 1 mM beta-glycerophosphate, 1 mM Na 3 VO 4 , 1 μg/mL leupeptin), phenylmethanesulfonyl fluoride (PMSF; Cell Signaling Technology) and a protease and phosphatase inhibitor cocktail (Boston BioProducts).…”

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confidence: 99%

A compendium of Amplification-Related Gain Of Sensitivity (ARGOS) genes in human cancer

Rendo,

Schubert,

Khuu

et al. 2023

Preprint

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Chromosomal gains are among the most frequent somatic genetic alterations occurring in cancer. While the effect of sustained oncogene expression has been characterized, the impact of copy-number gains affecting collaterally-amplified “bystander” genes on cellular fitness remains less understood. To investigate this, we built a comprehensive map of dosage compensations across human cancers by integrating expression and copy number profiles from over 8,000 TCGA tumors and CCLE cell lines. Further, we analyzed the effect of gene overexpression across 17 human cancer ORF screens to provide an overview of genes that prove toxic to cancer cells when overexpressed. Combining these two independent approaches we propose a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes. These genes are located in commonly amplified regions of the genome, have lower expression levels than expected by their copy-number status, and are toxic to cancer cells when overexpressed. We experimentally validatedCDKN1AandRBM14as high-confidence pan-cancer ARGOS genes in lung and breast cancer cell line models. We additionally suggest that RBM14’s mechanism of toxicity involves altered DNA damage response and innate immune signaling processes following gene overexpression. Finally, we provide a comprehensive catalog of compensated, toxic, and ARGOS genes as a community resource.

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Rbm14 maintains the integrity of genomic DNA during early mouse embryogenesis via mediating alternative splicing

Cited by 10 publications

References 49 publications

Study of FOXO1-interacting proteins using TurboID-based proximity labeling technology

Study of FOXO1-interacting proteins using TurboID-based proximity labeling technology

RBM14 Modulates Tubulin Acetylation and Regulates Spindle Morphology During Meiotic Maturation in Mouse Oocytes

A compendium of Amplification-Related Gain Of Sensitivity (ARGOS) genes in human cancer

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