Largen: A molecular regulator of mammalian cell size control

Kazuo Yamamoto, Valentina Gandin, Masato Sasaki, Susan McCracken, Wanda Li, Jennifer Liepa Silvester, Andrew J. Elia, Feng Wang, Yosuke Wakutani, Roumiana Alexandrova, Yathor D. Oo, Peter J. Mullen, Satoshi Inoue, Momoe Itsumi, Valentina Lapin, Jillian Haight, Andrew Wakeham, Arda Shahinian, Mitsuhiko Ikura, Ivan TopisirovicNahum Sonenberg, Tak W. Mak

Research output: Contribution to journalArticlepeer-review


Little is known about how mammalian cells maintain cell size homeostasis. We conducted a novel genetic screen to identify cell-size-controlling genes and isolated Largen, the product of a gene (PRR16) that increased cell size upon overexpression in human cells. Invitro evidence indicated that Largen preferentially stimulates the translation of specific subsetsof mRNAs, including those encoding proteins affecting mitochondrial functions. The involvement of Largen in mitochondrial respiration was consistentwith the increased mitochondrial mass and greater ATP production in Largen-overexpressing cells. Furthermore, Largen overexpression led to increased cell size invivo, as revealed by analyses of conditional Largen transgenic mice. Our results establish Largen as an important link between mRNA translation, mitochondrial functions, and the control of mammalian cell size.

Original languageEnglish
Pages (from-to)904-915
Number of pages12
JournalMolecular Cell
Issue number6
Publication statusPublished - 2014 Mar 20
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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