RBM15 condensates modulate m6A modification of STYK1 to promote tumorigenesis

Jiang, Amin; Zhang, Siwei; Wang, Xinyu; Liu, Dong

doi:10.1016/j.csbj.2022.08.068

Cited by 9 publications

(5 citation statements)

References 60 publications

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“…466 Most importantly, RBM15 condensates promote the m 6 A modification of the transcripts of highly expressing cancer-related genes and are partially colocalized with m 6 A-modified transcripts in the nucleus. 466 In myeloid leukemia, m 6 A is found to be required for YTHDC1 to undergo LLPS, generating nuclear YTHDC1-m 6 A condensates to maintain cell survival and myeloid leukemic undifferentiated state. 324 METTL3 can also undergo LLPS, and its self-interacting ability provides the necessary multivalency for LLPS of mRNA m 6 A methyltransferase complex.…”

Section: Rna Modifications Regulate Llps To Affect Disease Developmentmentioning

confidence: 99%

“…IGF2BP1 is an important m 6 A modulatory gene that has always increased in many malignant tissues. RBM15 contains IDR and potentially forms “liquid‐like” condensates in vivo and in vitro 466 . RBM15 condensates are prone to contact or partially overlap with nuclear speckles rather than other membraneless chambers 466 .…”

Section: Synergy Of Llps and Rna Modifications In Diseasesmentioning

confidence: 99%

“…RBM15 contains IDR and potentially forms “liquid‐like” condensates in vivo and in vitro 466 . RBM15 condensates are prone to contact or partially overlap with nuclear speckles rather than other membraneless chambers 466 . Most importantly, RBM15 condensates promote the m 6 A modification of the transcripts of highly expressing cancer‐related genes and are partially colocalized with m 6 A‐modified transcripts in the nucleus 466 .…”

Section: Synergy Of Llps and Rna Modifications In Diseasesmentioning

confidence: 99%

“…RBM15 condensates are prone to contact or partially overlap with nuclear speckles rather than other membraneless chambers 466 . Most importantly, RBM15 condensates promote the m 6 A modification of the transcripts of highly expressing cancer‐related genes and are partially colocalized with m 6 A‐modified transcripts in the nucleus 466 . In myeloid leukemia, m 6 A is found to be required for YTHDC1 to undergo LLPS, generating nuclear YTHDC1–m 6 A condensates to maintain cell survival and myeloid leukemic undifferentiated state 324 .…”

Section: Synergy Of Llps and Rna Modifications In Diseasesmentioning

confidence: 99%

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Liquid–liquid phase separation in diseases

Zhang,

Yuan,

Zhang

et al. 2024

MedComm

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Liquid–liquid phase separation (LLPS), an emerging biophysical phenomenon, can sequester molecules to implement physiological and pathological functions. LLPS implements the assembly of numerous membraneless chambers, including stress granules and P‐bodies, containing RNA and protein. RNA–RNA and RNA–protein interactions play a critical role in LLPS. Scaffolding proteins, through multivalent interactions and external factors, support protein–RNA interaction networks to form condensates involved in a variety of diseases, particularly neurodegenerative diseases and cancer. Modulating LLPS phenomenon in multiple pathogenic proteins for the treatment of neurodegenerative diseases and cancer could present a promising direction, though recent advances in this area are limited. Here, we summarize in detail the complexity of LLPS in constructing signaling pathways and highlight the role of LLPS in neurodegenerative diseases and cancers. We also explore RNA modifications on LLPS to alter diseases progression because these modifications can influence LLPS of certain proteins or the formation of stress granules, and discuss the possibility of proper manipulation of LLPS process to restore cellular homeostasis or develop therapeutic drugs for the eradication of diseases. This review attempts to discuss potential therapeutic opportunities by elaborating on the connection between LLPS, RNA modification, and their roles in diseases.

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Section: Rna Modifications Regulate Llps To Affect Disease Developmentmentioning

confidence: 99%

Section: Synergy Of Llps and Rna Modifications In Diseasesmentioning

confidence: 99%

Section: Synergy Of Llps and Rna Modifications In Diseasesmentioning

confidence: 99%

Section: Synergy Of Llps and Rna Modifications In Diseasesmentioning

confidence: 99%

See 2 more Smart Citations

Liquid–liquid phase separation in diseases

Zhang,

Yuan,

Zhang

et al. 2024

MedComm

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“…Recent studies have revealed the involvement of RBM15 in cellular biological behaviors such as proliferation, invasion, migration, and apoptosis in various cancers, like acute megakaryocytic leukemia ( 36 ), colorectal cancer ( 37 ), ovarian cancer ( 38 ), laryngeal squamous cell carcinoma ( 25 ) and osteosarcoma ( 39 ). High expression levels of RBM15 are typically correlated with a poor prognosis in patients with malignancies ( 40 ). In this review, we will focus on the individual function of RBM15 and its related mechanisms, highlighting the current status of RBM15 regulatory mechanisms in tumors and providing researchers with new ideas for tumor therapy.…”

Section: Introductionmentioning

confidence: 99%

Exploring the role of m 6 A writer RBM15 in cancer: a systematic review

Cao,

Qiu,

Dong

et al. 2024

Front. Oncol.

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In the contemporary epoch, cancer stands as the predominant cause of premature global mortality, necessitating a focused exploration of molecular markers and advanced therapeutic strategies. N6-methyladenosine (m6A), the most prevalent mRNA modification, undergoes dynamic regulation by enzymes referred to as methyltransferases (writers), demethylases (erasers), and effective proteins (readers). Despite lacking methylation activity, RNA-binding motif protein 15 (RBM15), a member of the m6A writer family, assumes a crucial role in recruiting the methyltransferase complex (MTC) and binding to mRNA. Although the impact of m6A modifications on cancer has garnered widespread attention, RBM15 has been relatively overlooked. This review briefly outlines the structure and operational mechanism, and delineates the unique role of RBM15 in various cancers, shedding light on its molecular basis and providing a groundwork for potential tumor-targeted therapies.

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Role of liquid–liquid phase separation in cancer: Mechanisms and therapeutic implications

Li,

2024

Cancer Innovation

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Liquid–liquid phase separation (LLPS) has emerged as a pivotal biological phenomenon involved in various cellular processes, including the formation of membrane‐less organelles and the regulation of biomolecular condensates through precise spatiotemporal coordination of signaling pathways in cells. Dysregulation of LLPSs results in aberrant biomolecular condensates, which are widely implicated in tumorigenesis and cancer progression. Here, we comprehensively summarize the multifaceted roles of LLPS in tumor biology from the perspective of cancer hallmarks, including genomic stability, metabolic reprogramming progression, ferroptosis, and metastasis, to unveil the intricate mechanisms by which LLPS occurs in tumorigenesis. We discuss current discoveries related to therapeutic involvement and potential clinical applications of LLPS in cancer treatment, highlighting the potential of targeting LLPS‐driven processes as novel therapeutic strategies. Additionally, we discuss the challenges associated with new approaches for cancer treatment based on LLPS. This in‐depth discussion of the impact of LLPS on fundamental aspects of tumor biology provides new insights into overcoming cancer.

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RBM15 condensates modulate m6A modification of STYK1 to promote tumorigenesis

Cited by 9 publications

References 60 publications

Liquid–liquid phase separation in diseases

Liquid–liquid phase separation in diseases

Exploring the role of m 6 A writer RBM15 in cancer: a systematic review

Role of liquid–liquid phase separation in cancer: Mechanisms and therapeutic implications

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