RNA-Binding Protein L1TD1 Interacts with LIN28 via RNA and is Required for Human Embryonic Stem Cell Self-Renewal and Cancer Cell Proliferation§

Authors


  • Author contributions: E.N. and N.R.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and responsibility for the integrity of the work as a whole, from inception to published article; M.R.E. and J.-P.P.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; R.Lu.: conception and design, data analysis and interpretation, and manuscript writing; J.N.: collection and assembly of data; R.A., K.D., and H.L.: data analysis and interpretation; O.R.: molecular biology and construct design; A.R.: conception and design, interpretation of results, and manuscript writing; R.L.: conception and design, interpretation of results, leader and supervision of the project, and manuscript writing. E.N., N.R., and M.R.E. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS December 12, 2011.

Abstract

Human embryonic stem cells (hESC) have a unique capacity to self-renew and differentiate into all the cell types found in human body. Although the transcriptional regulators of pluripotency are well studied, the role of cytoplasmic regulators is still poorly characterized. Here, we report a new stem cell-specific RNA-binding protein L1TD1 (ECAT11, FLJ10884) required for hESC self-renewal and cancer cell proliferation. Depletion of L1TD1 results in immediate downregulation of OCT4 and NANOG. Furthermore, we demonstrate that OCT4, SOX2, and NANOG all bind to the promoter of L1TD1. Moreover, L1TD1 is highly expressed in seminomas, and depletion of L1TD1 in these cancer cells influences self-renewal and proliferation. We show that L1TD1 colocalizes and interacts with LIN28 via RNA and directly with RNA helicase A (RHA). LIN28 has been reported to regulate translation of OCT4 in complex with RHA. Thus, we hypothesize that L1TD1 is part of the L1TD1-RHA-LIN28 complex that could influence levels of OCT4. Our results strongly suggest that L1TD1 has an important role in the regulation of stemness. STEM CELLS 2012;30:452–460

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