The mammalian ecdysoneless protein interacts with RNA helicase DDX39A to regulate nuclear mRNA export

Irfana Saleem, Sameer Mirza, Aniruddha Sarkar, Mohsin Raza, Bhopal Mohapatra, Insha Mushtaq, Jun Hyun Kim, Nitish K. Mishra, Mansour A. Alsaleem, Emad A. Rakha, Fang Qiu, Chittibabu Guda, Hamid Band, Vimla Band

Research output: Contribution to journalArticlepeer-review

Abstract

The mammalian orthologue of ecdysoneless (ECD) protein is required for embryogenesis, cell cycle progression, and mitigation of endoplasmic reticulum stress. Here, we identified key components of the mRNA export complexes as binding partners of ECD and characterized the functional interaction of ECD with key mRNA export-related DEAD BOX protein helicase DDX39A. We find that ECD is involved in RNA export through its interaction with DDX39A. ECD knockdown (KD) blocks mRNA export from the nucleus to the cytoplasm, which is rescued by expression of full-length ECD but not an ECD mutant that is defective in interaction with DDX39A. We have previously shown that ECD protein is overexpressed in ErbB21 breast cancers (BC). In this study, we extended the analyses to two publicly available BC mRNA The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data sets. In both data sets, ECD mRNA overexpression correlated with short patient survival, specifically ErbB21 BC. In the METABRIC data set, ECD overexpression also correlated with poor patient survival in triple-negative breast cancer (TNBC). Furthermore, ECD KD in ErbB21 BC cells led to a decrease in ErbB2 mRNA level due to a block in its nuclear export and was associated with impairment of oncogenic traits. These findings provide novel mechanistic insight into the physiological and pathological functions of ECD.

Original languageEnglish (US)
Article numbere00103-21
JournalMolecular and cellular biology
Volume41
Issue number7
DOIs
StatePublished - Jun 2021

Keywords

  • ECD
  • Ecdysoneless
  • ErbB2
  • HSGT1
  • Oncogenesis
  • RNA export
  • RNA helicase
  • RNA processing
  • RNA splicing

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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