eIF4E is a central node of an RNA regulon that governs cellular proliferation.
This study demonstrates that the eukaryotic translation initiation factor eIF4E is a critical node in an RNA regulon that impacts nearly every stage of cell cycle progression. Specifically, eIF4E coordinately promotes the messenger RNA (mRNA) export of several genes involved in the cell cycle. A common feature of these mRNAs is a structurally conserved, approximately 50-nucleotide element in the 3' untranslated region denoted as an eIF4E sensitivity element. This element is sufficient for localization of capped mRNAs to eIF4E nuclear bodies, formation of eIF4E-specific ribonucleoproteins in the nucleus, and eIF4E-dependent mRNA export. The roles of eIF4E in translation and mRNA export are distinct, as they rely on different mRNA elements. Furthermore, eIF4E-dependent mRNA export is independent of ongoing RNA or protein synthesis. Unlike the NXF1-mediated export of bulk mRNAs, eIF4E-dependent mRNA export is CRM1 dependent. Finally, the growth-suppressive promyelocytic leukemia protein (PML) inhibits this RNA regulon. These data provide novel perspectives into the proliferative and oncogenic properties of eIF4E.
Culjkovic
Biljana
B
Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H4M 1J6, Canada.
Topisirovic
Ivan
I
Skrabanek
Lucy
L
Ruiz-Gutierrez
Melisa
M
Borden
Katherine L B
KL
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D022003:Cell Nucleus Structures / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D018085:Regulon; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020298:U937 Cells; D020506:Untranslated Regions / Q000378:metabolism; D000097606:Exportin 1 Protein
D018797:Cell Cycle Proteins; D019938:Cyclin D1; D039561:Eukaryotic Initiation Factor-4E; D028884:Karyopherins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D000071156:Promyelocytic Leukemia Protein; D051573:Proto-Oncogene Proteins c-pim-1; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D020506:Untranslated Regions; D000097606:Exportin 1 Protein; C122111:NXF1 protein, human; C070576:PML protein, human