title: RNA-binding protein L1TD1 interacts with LIN28 via RNA and is required for human embryonic stem cell self-renewal and cancer cell proliferation.
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.
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Närvä
authors.forename: Nelly
authors.initials: N
authors.lastname: Rahkonen
authors.forename: Maheswara Reddy
authors.initials: MR
authors.lastname: Emani
authors.forename: Riikka
authors.initials: R
authors.lastname: Lund
authors.forename: Juha-Pekka
authors.initials: JP
authors.lastname: Pursiheimo
authors.forename: Juuso
authors.initials: J
authors.lastname: Nästi
authors.forename: Reija
authors.initials: R
authors.lastname: Autio
authors.forename: Omid
authors.initials: O
authors.lastname: Rasool
authors.forename: Konstantin
authors.initials: K
authors.lastname: Denessiouk
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D054278:Embryonal Carcinoma Stem Cells / Q000378:metabolism / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018239:Seminoma / Q000378:metabolism / Q000473:pathology
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; C562346:L1TD1 protein, human; C000715187:Lin28A protein, human; D009363:Neoplasm Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D012313:RNA; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases