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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
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Alternatively Splicing Interactomes Identify Novel Isoform-Specific Partners for NSD2.

Weidi Wang1,2, Yucan Chen1, Jingjing Zhao1

  • 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Frontiers in Cell and Developmental Biology
|March 15, 2021
PubMed
Summary

Nuclear receptor SET domain protein (NSD2) isoform-specific interactions were mapped, revealing novel protein partners crucial for understanding Wolf-Hirschhorn Syndrome and myeloma development.

Keywords:
NSD2RPL10alternatively splicingisoformprotein–protein interaction

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Nuclear receptor SET domain protein (NSD2) is implicated in Wolf-Hirschhorn Syndrome and human myelomas.
  • Understanding NSD2's protein-protein interaction (PPI) patterns at the isoform/exon level is limited.

Purpose of the Study:

  • To explore the isoform-specific protein-protein interaction (PPI) landscape of Nuclear receptor SET domain protein (NSD2).
  • To identify novel NSD2 interacting partners and their roles in disease pathogenesis.

Main Methods:

  • Immunofluorescence microscopy to determine subcellular localization of NSD2 transcripts.
  • Label-free quantification immunoprecipitation mass spectrometry (IP-MS) to identify PPI partners.
  • Co-immunoprecipitation and Western blotting for validation of identified interactions.

Main Results:

  • Identified 890 novel isoform-specific PPI partners for NSD2 (83% novel).
  • Discovered exon-specific interactomes, with RPL10 and HSPA8 confirmed as interacting partners.
  • RPL10 interacted with NSD2 Isoforms 1, 3, and 5; HSPA8 interacted with all four isoforms.

Conclusions:

  • Generated an isoform-level PPI landscape for NSD2, providing reference interactome data.
  • The identified interactions shed light on NSD2's diverse roles in RNA splicing, WHS, and myeloma.
  • Findings offer a basis for developing treatments for NSD2-related developmental diseases.