The RNA-Binding Motif Protein Family in Cancer: Friend or Foe?

Li, Zhigang; Guo, Qingyu; Zhang, Jiaxin; Fu, Zitong; Wang, Yifei; Wang, Tianzhen; Tang, Jing

doi:10.3389/fonc.2021.757135

Cited by 39 publications

(31 citation statements)

References 75 publications

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“…SRSF5 is overexpressed in lung cancer and colorectal cancer tissues. , PRPF40B, a splicing processing factor, is underexpressed in acute myeloid leukemia . RBMX and its related proteins are involved in multiple cancers, such as bladder cancer and hepatocellular cancer. − HNRNPA1, a multipurpose RNA-binding protein and splicing factor, is also highly associated with cancer and can regulate many alternative splicing events . For example, HNRNPA1 is an oncogenic driver in glioblastoma .…”

Section: Resultsmentioning

confidence: 99%

IQGAP1 and RNA Splicing in the Context of Head and Neck via Phosphoproteomics

et al. 2022

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IQGAP1 (IQ motif-containing GTPase-activating protein 1) scaffolds several signaling pathways in mammalian cells that are implicated in carcinogenesis, including the RAS and PI3K pathways that involve multiple protein kinases. IQGAP1 has been shown to promote head and neck squamous cell carcinoma (HNSCC); however, the underlying mechanism(s) remains unclear. Here, we report a mass spectrometry-based analysis identifying differences in phosphorylation of cellular proteins in vivo and in vitro in the presence or absence of IQGAP1. By comparing the esophageal phosphoproteome profiles between Iqgap1 +/+ and Iqgap1 −/− mice, we identified RNA splicing as one of the most altered cellular processes. Serine/arginine-rich splicing factor 6 (SRSF6) was the protein with the most downregulated levels of phosphorylation in Iqgap1 −/− tissue. We confirmed that the absence of IQGAP1 reduced SRSF6 phosphorylation both in vivo and in vitro. We then expanded our analysis to human normal oral keratinocytes. Again, we found factors involved in RNA splicing to be highly altered in the phosphoproteome profile upon genetic disruption of IQGAP1. Both the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Cancer Genome Atlas (TCGA) data sets indicate that phosphorylation of splicing-related proteins is important in HNSCC prognosis. The Biological General Repository for Interaction Datasets (BioGRID) repository also suggested multiple interactions between IQGAP1 and splicingrelated proteins. Based on these collective observations, we propose that IQGAP1 regulates the phosphorylation of splicing proteins, which potentially affects their splicing activities and, therefore, contributes to HNSCC. Raw data are available from the MassIVE database with identifier MSV000087770.

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Section: Resultsmentioning

confidence: 99%

IQGAP1 and RNA Splicing in the Context of Head and Neck via Phosphoproteomics

et al. 2022

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“…RNA binding motif (RBM) proteins represent a complex family comprised by proteins that can either fuel cancer progression or suppress tumor development and/or progression (54,55).…”

Section: Discussionmentioning

confidence: 99%

“…Molecularly, although the main function of RBM proteins is the regulation of splicing process (54), some of them can also regulate transcription, therefore controlling a plethora of signaling pathways (28,56). This is the case of RBM22, which has an RNA Recognition Motif (RRM) but also a Zinc-Finger like domain (28).…”

Section: Discussionmentioning

confidence: 99%

Tumor suppressor role of RBM22 in prostate cancer acting as a dual-factor regulating alternative splicing and transcription of key oncogenic genes

Jiménez‐Vacas

Montero-Hidalgo²,

Gómez‐Gómez³

et al. 2023

Translational Research

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“…This inevitably leads to a large number of diseases when their function is altered. Recently, Li and coworkers reviewed the role played by RBM members in cancer [140].…”

Section: The Functions Of Rbm Proteins In Rna-related Metabolismmentioning

confidence: 99%

RBM22, a Key Player of Pre-mRNA Splicing and Gene Expression Regulation, Is Altered in Cancer

Soubise

Jiang

Douet‐Guilbert

et al. 2022

Cancers

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RNA-Binding Proteins (RBP) are very diverse and cover a large number of functions in the cells. This review focuses on RBM22, a gene encoding an RBP and belonging to the RNA-Binding Motif (RBM) family of genes. RBM22 presents a Zinc Finger like and a Zinc Finger domain, an RNA-Recognition Motif (RRM), and a Proline-Rich domain with a general structure suggesting a fusion of two yeast genes during evolution: Cwc2 and Ecm2. RBM22 is mainly involved in pre-mRNA splicing, playing the essential role of maintaining the conformation of the catalytic core of the spliceosome and acting as a bridge between the catalytic core and other essential protein components of the spliceosome. RBM22 is also involved in gene regulation, and is able to bind DNA, acting as a bona fide transcription factor on a large number of target genes. Undoubtedly due to its wide scope in the regulation of gene expression, RBM22 has been associated with several pathologies and, notably, with the aggressiveness of cancer cells and with the phenotype of a myelodysplastic syndrome. Mutations, enforced expression level, and haploinsufficiency of RBM22 gene are observed in those diseases. RBM22 could represent a potential therapeutic target in specific diseases, and, notably, in cancer.

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The RNA-Binding Motif Protein Family in Cancer: Friend or Foe?

Cited by 39 publications

References 75 publications

IQGAP1 and RNA Splicing in the Context of Head and Neck via Phosphoproteomics

IQGAP1 and RNA Splicing in the Context of Head and Neck via Phosphoproteomics

Tumor suppressor role of RBM22 in prostate cancer acting as a dual-factor regulating alternative splicing and transcription of key oncogenic genes

RBM22, a Key Player of Pre-mRNA Splicing and Gene Expression Regulation, Is Altered in Cancer

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