RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site

Jasmine George; Yongsheng Li; Ishaque P. Kadamberi; Deepak Parashar; Shirng Wern Tsaih; Prachi Gupta; Anjali Geethadevi; Changliang Chen; Chandrima Ghosh; Yunguang Sun; Sonam Mittal; Ramani Ramchandran; Hallgeir Rui; Gabriel Lopez-Berestein; Cristian Rodriguez-Aguayo; Gustavo Leone; Janet S. Rader; Anil K. Sood; Madhusudan Dey; Sunila Pradeep; Pradeep Chaluvally-Raghavan

doi:10.1016/j.celrep.2021.109934

RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site

Jasmine George, Yongsheng Li, Ishaque P. Kadamberi, Deepak Parashar, Shirng Wern Tsaih, Prachi Gupta, Anjali Geethadevi, Changliang Chen, Chandrima Ghosh, Yunguang Sun, Sonam Mittal, Ramani Ramchandran, Hallgeir Rui, Gabriel Lopez-Berestein, Cristian Rodriguez-Aguayo, Gustavo Leone, Janet S. Rader, Anil K. Sood, Madhusudan Dey, Sunila PradeepPradeep Chaluvally-Raghavan

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Fragile X-related protein-1 (FXR1) gene is highly amplified in patients with ovarian cancer, and this amplification is associated with increased expression of both FXR1 mRNA and protein. FXR1 expression directly associates with the survival and proliferation of cancer cells. Surface sensing of translation (SUnSET) assay demonstrates that FXR1 enhances the overall translation in cancer cells. Reverse-phase protein array (RPPA) reveals that cMYC is the key target of FXR1. Mechanistically, FXR1 binds to the AU-rich elements (ARE) present within the 3′ untranslated region (3′UTR) of cMYC and stabilizes its expression. In addition, the RGG domain in FXR1 interacts with eIF4A1 and eIF4E proteins. These two interactions of FXR1 result in the circularization of cMYC mRNA and facilitate the recruitment of eukaryotic translation initiation factors to the translation start site. In brief, we uncover a mechanism by which FXR1 promotes cMYC levels in cancer cells.

Original language	English (US)
Article number	109934
Journal	Cell Reports
Volume	37
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2021.109934
State	Published - Nov 2 2021

Keywords

ARE
CNV
EIF4F
FXR1
SUnSET
cMYC
eIFs
mRNA circularization
ovarian cancer
translation

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Cytogenetics and Cell Authentication Core
Functional Proteomics Reverse Phase Protein Array Core
Bioinformatics Shared Resource

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10.1016/j.celrep.2021.109934

Cite this

George, J., Li, Y., Kadamberi, I. P., Parashar, D., Tsaih, S. W., Gupta, P., Geethadevi, A., Chen, C., Ghosh, C., Sun, Y., Mittal, S., Ramchandran, R., Rui, H., Lopez-Berestein, G., Rodriguez-Aguayo, C., Leone, G., Rader, J. S., Sood, A. K., Dey, M., ... Chaluvally-Raghavan, P. (2021). RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site. Cell Reports, 37(5), Article 109934. https://doi.org/10.1016/j.celrep.2021.109934

George, J, Li, Y, Kadamberi, IP, Parashar, D, Tsaih, SW, Gupta, P, Geethadevi, A, Chen, C, Ghosh, C, Sun, Y, Mittal, S, Ramchandran, R, Rui, H, Lopez-Berestein, G , Rodriguez-Aguayo, C, Leone, G, Rader, JS, Sood, AK, Dey, M, Pradeep, S & Chaluvally-Raghavan, P 2021, 'RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site', Cell Reports, vol. 37, no. 5, 109934. https://doi.org/10.1016/j.celrep.2021.109934

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title = "RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site",

abstract = "Fragile X-related protein-1 (FXR1) gene is highly amplified in patients with ovarian cancer, and this amplification is associated with increased expression of both FXR1 mRNA and protein. FXR1 expression directly associates with the survival and proliferation of cancer cells. Surface sensing of translation (SUnSET) assay demonstrates that FXR1 enhances the overall translation in cancer cells. Reverse-phase protein array (RPPA) reveals that cMYC is the key target of FXR1. Mechanistically, FXR1 binds to the AU-rich elements (ARE) present within the 3′ untranslated region (3′UTR) of cMYC and stabilizes its expression. In addition, the RGG domain in FXR1 interacts with eIF4A1 and eIF4E proteins. These two interactions of FXR1 result in the circularization of cMYC mRNA and facilitate the recruitment of eukaryotic translation initiation factors to the translation start site. In brief, we uncover a mechanism by which FXR1 promotes cMYC levels in cancer cells.",

keywords = "ARE, CNV, EIF4F, FXR1, SUnSET, cMYC, eIFs, mRNA circularization, ovarian cancer, translation",

author = "Jasmine George and Yongsheng Li and Kadamberi, {Ishaque P.} and Deepak Parashar and Tsaih, {Shirng Wern} and Prachi Gupta and Anjali Geethadevi and Changliang Chen and Chandrima Ghosh and Yunguang Sun and Sonam Mittal and Ramani Ramchandran and Hallgeir Rui and Gabriel Lopez-Berestein and Cristian Rodriguez-Aguayo and Gustavo Leone and Rader, {Janet S.} and Sood, {Anil K.} and Madhusudan Dey and Sunila Pradeep and Pradeep Chaluvally-Raghavan",

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year = "2021",

month = nov,

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doi = "10.1016/j.celrep.2021.109934",

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T1 - RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site

AU - George, Jasmine

AU - Li, Yongsheng

AU - Kadamberi, Ishaque P.

AU - Parashar, Deepak

AU - Tsaih, Shirng Wern

AU - Gupta, Prachi

AU - Geethadevi, Anjali

AU - Chen, Changliang

AU - Ghosh, Chandrima

AU - Sun, Yunguang

AU - Mittal, Sonam

AU - Ramchandran, Ramani

AU - Rui, Hallgeir

AU - Lopez-Berestein, Gabriel

AU - Rodriguez-Aguayo, Cristian

AU - Leone, Gustavo

AU - Rader, Janet S.

AU - Sood, Anil K.

AU - Dey, Madhusudan

AU - Pradeep, Sunila

AU - Chaluvally-Raghavan, Pradeep

PY - 2021/11/2

Y1 - 2021/11/2

N2 - Fragile X-related protein-1 (FXR1) gene is highly amplified in patients with ovarian cancer, and this amplification is associated with increased expression of both FXR1 mRNA and protein. FXR1 expression directly associates with the survival and proliferation of cancer cells. Surface sensing of translation (SUnSET) assay demonstrates that FXR1 enhances the overall translation in cancer cells. Reverse-phase protein array (RPPA) reveals that cMYC is the key target of FXR1. Mechanistically, FXR1 binds to the AU-rich elements (ARE) present within the 3′ untranslated region (3′UTR) of cMYC and stabilizes its expression. In addition, the RGG domain in FXR1 interacts with eIF4A1 and eIF4E proteins. These two interactions of FXR1 result in the circularization of cMYC mRNA and facilitate the recruitment of eukaryotic translation initiation factors to the translation start site. In brief, we uncover a mechanism by which FXR1 promotes cMYC levels in cancer cells.

AB - Fragile X-related protein-1 (FXR1) gene is highly amplified in patients with ovarian cancer, and this amplification is associated with increased expression of both FXR1 mRNA and protein. FXR1 expression directly associates with the survival and proliferation of cancer cells. Surface sensing of translation (SUnSET) assay demonstrates that FXR1 enhances the overall translation in cancer cells. Reverse-phase protein array (RPPA) reveals that cMYC is the key target of FXR1. Mechanistically, FXR1 binds to the AU-rich elements (ARE) present within the 3′ untranslated region (3′UTR) of cMYC and stabilizes its expression. In addition, the RGG domain in FXR1 interacts with eIF4A1 and eIF4E proteins. These two interactions of FXR1 result in the circularization of cMYC mRNA and facilitate the recruitment of eukaryotic translation initiation factors to the translation start site. In brief, we uncover a mechanism by which FXR1 promotes cMYC levels in cancer cells.

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KW - EIF4F

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KW - translation

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RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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