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RBM4 modulates the proliferation and expression of inflammatory factors via the alternative splicing of regulatory factors in HeLa cells

  • Wei-Yang Wang
  • Weili Quan
  • Fan Yang
  • Ya-Xun Wei
  • Jia-Jun Chen
  • Han Yu
  • Jie Xie
  • Yi Zhang
  • Zhan-Fei LiEmail author
Original Article

Abstract

Regulatory factors function by modulating a variety of cascade mechanisms in cells. RBM4 is a multifunctional RNA-binding protein in post-transcriptional gene regulation. Cytoplasmic RBM4 interacts with Ago2 to regulate inflammatory responses by affecting mRNA decay and cap-dependent translation. However, it is unclear whether RBM4 functions in inflammation regulation by its splicing factor role. Here, the cell biology, gene expression profile and alternative splicing pattern of HeLa cells with RBM4 overexpression (RBM-OE) were compared with the control. The results showed that RBM4-OE inhibited proliferation. RBM4-OE extensively affects the transcriptional level of genes involved in cell surface receptor signalling pathway, inflammatory responses and the response to lipopolysaccharide. RBM4 broadly regulated the alternative splicing of hundreds of genes with functions of protein binding, helicase activity, DNA binding and transcription co-activator. RBM4-regulated splicing of these genes plays an important role in apoptotic process and gene transcription regulation. As an example, exon inclusion of TNIP1 mediated by RBM4 affects the expression of its targets in inflammatory pathways. These results indicated that RBM4 can mediate the inflammatory response via splicing regulation, which adds to the understanding of the critical role of RBM4 in cancer complicated by inflammation. In conclusion, this study indicated a mechanism in which the dysregulation of alternative splicing can influence cellular biology and lead to various immune-related diseases.

Keywords

RBM4 Overexpression Gene expression profile Differentially expressed genes Inflammatory response Alternative splicing 

Notes

Acknowledgements

This study was partially supported by ABLife (ABL-7702098).

Compliance with ethical standards

Conflict of interest

All the authors declare that he/she has no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Wei-Yang Wang
    • 1
  • Weili Quan
    • 2
    • 3
  • Fan Yang
    • 1
  • Ya-Xun Wei
    • 2
  • Jia-Jun Chen
    • 1
  • Han Yu
    • 3
  • Jie Xie
    • 1
  • Yi Zhang
    • 2
    • 3
  • Zhan-Fei Li
    • 1
    Email author
  1. 1.Trama Center/Department of Emergency and Trauma Surgery, Tongji Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Center for Genome AnalysisABLife Inc.WuhanChina
  3. 3.Laboratory for Genome Regulation and Human HealthABLife Inc.WuhanChina

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