PMID- 33941617 OWN - NLM STAT- MEDLINE DCOM- 20210720 LR - 20211224 IS - 1098-5549 (Electronic) IS - 0270-7306 (Print) IS - 0270-7306 (Linking) VI - 41 IP - 7 DP - 2021 Jun 23 TI - The Mammalian Ecdysoneless Protein Interacts with RNA Helicase DDX39A To Regulate Nuclear mRNA Export. PG - e0010321 LID - 10.1128/MCB.00103-21 [doi] LID - e00103-21 AB - 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 ErbB2(+) 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 ErbB2(+) BC. In the METABRIC data set, ECD overexpression also correlated with poor patient survival in triple-negative breast cancer (TNBC). Furthermore, ECD KD in ErbB2(+) 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. FAU - Saleem, Irfana AU - Saleem I AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Mirza, Sameer AU - Mirza S AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Sarkar, Aniruddha AU - Sarkar A AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Raza, Mohsin AU - Raza M AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Mohapatra, Bhopal AU - Mohapatra B AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Mushtaq, Insha AU - Mushtaq I AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Kim, Jun Hyun AU - Kim JH AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Mishra, Nitish K AU - Mishra NK AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Alsaleem, Mansour A AU - Alsaleem MA AD - Department of Pathology, School of Medicine, University of Nottingham, Nottingham, United Kingdom. FAU - Rakha, Emad A AU - Rakha EA AD - Department of Pathology, School of Medicine, University of Nottingham, Nottingham, United Kingdom. FAU - Qiu, Fang AU - Qiu F AD - Department of Biostatistics, University of Nebraska Medical Center, Omaha, Nebraska, USA. AD - Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Guda, Chittibabu AU - Guda C AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. AD - Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Band, Hamid AU - Band H AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA. AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA. AD - Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center Omaha, Nebraska, USA. AD - Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Band, Vimla AU - Band V AD - Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA. AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA. AD - Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, USA. LA - eng GR - P30 CA036727/CA/NCI NIH HHS/United States GR - R21 CA241055/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20210623 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Carrier Proteins) RN - 0 (RNA, Messenger) RN - EC 3.6.1.- (DDX39A protein, human) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM MH - Active Transport, Cell Nucleus/*physiology MH - Animals MH - Carrier Proteins/metabolism MH - Cytoplasm/metabolism MH - DEAD-box RNA Helicases/*metabolism MH - Gene Expression/genetics MH - Humans MH - RNA Splicing/genetics MH - RNA Transport/genetics/*physiology MH - RNA, Messenger/*metabolism MH - Triple Negative Breast Neoplasms/metabolism PMC - PMC8224239 OTO - NOTNLM OT - ECD OT - ErbB2 OT - RNA export OT - RNA helicase OT - RNA processing OT - RNA splicing OT - ecdysoneless OT - hSGT1 OT - oncogenesis EDAT- 2021/05/05 06:00 MHDA- 2021/07/21 06:00 PMCR- 2021/12/23 CRDT- 2021/05/04 06:25 PHST- 2021/05/05 06:00 [pubmed] PHST- 2021/07/21 06:00 [medline] PHST- 2021/05/04 06:25 [entrez] PHST- 2021/12/23 00:00 [pmc-release] AID - MCB.00103-21 [pii] AID - 00103-21 [pii] AID - 10.1128/MCB.00103-21 [doi] PST - ppublish SO - Mol Cell Biol. 2021 Jun 23;41(7):e0010321. doi: 10.1128/MCB.00103-21. Epub 2021 Jun 23.