Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation

Arnaldo Carreira-Rosario, Varsha Bhargava, Jens Hillebrand, Rahul K. Kollipara, Mani Ramaswami, Michael Buszczak

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

RNA-binding Fox (Rbfox) proteins have well-established roles in regulating alternative splicing, but specific Rbfox isoforms lack nuclear localization signals and accumulate in the cytoplasm. The potential splicing-independent functions of these proteins remain unknown. Here we demonstrate that cytoplasmic Drosophila Rbfox1 regulates germ cell development and represses the translation of mRNAs containing (U)GCAUG elements within their 3'UTRs. During germline cyst differentiation, Rbfox1 targets pumilio mRNA for destabilization and translational silencing, thereby promoting germ cell development. Mis-expression of pumilio results in the formation of germline tumors, which contain cysts that break down and dedifferentiate back to single, mitotically active cells. Together, these results reveal that cytoplasmic Rbfox family members regulate the translation of specific target mRNAs. In the Drosophila ovary, this activity provides a genetic barrier that prevents germ cells from reverting back to an earlier developmental state. The finding that Rbfox proteins regulate mRNA translation has implications for Rbfox-related diseases.

Original languageEnglish (US)
Pages (from-to)562-571
Number of pages10
JournalDevelopmental Cell
Volume36
Issue number5
DOIs
StatePublished - Mar 7 2016

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Germ Cells
Cell Differentiation
RNA-Binding Proteins
Cells
Protein Biosynthesis
RNA
Drosophila
Cysts
Messenger RNA
Nuclear Localization Signals
Proteins
Alternative Splicing
3' Untranslated Regions
Ovary
Protein Isoforms
Cytoplasm
Tumors
Neoplasms
Carrier Proteins

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Carreira-Rosario, A., Bhargava, V., Hillebrand, J., Kollipara, R. K., Ramaswami, M., & Buszczak, M. (2016). Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation. Developmental Cell, 36(5), 562-571. https://doi.org/10.1016/j.devcel.2016.02.010

Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation. / Carreira-Rosario, Arnaldo; Bhargava, Varsha; Hillebrand, Jens; Kollipara, Rahul K.; Ramaswami, Mani; Buszczak, Michael.

In: Developmental Cell, Vol. 36, No. 5, 07.03.2016, p. 562-571.

Research output: Contribution to journalArticle

Carreira-Rosario, A, Bhargava, V, Hillebrand, J, Kollipara, RK, Ramaswami, M & Buszczak, M 2016, 'Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation', Developmental Cell, vol. 36, no. 5, pp. 562-571. https://doi.org/10.1016/j.devcel.2016.02.010
Carreira-Rosario, Arnaldo ; Bhargava, Varsha ; Hillebrand, Jens ; Kollipara, Rahul K. ; Ramaswami, Mani ; Buszczak, Michael. / Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation. In: Developmental Cell. 2016 ; Vol. 36, No. 5. pp. 562-571.
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