Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1.
We used computational algorithms to find conserved sequences in the 3' untranslated region (UTR) of transcripts that exhibited rapid decay in primary human T cells and found that the consensus sequence UGUUUGUUUGU, which we have termed a GU-rich element (GRE), was enriched in short-lived transcripts. Using a tet-off reporter system, we showed that insertion of GRE-containing sequences from c-jun, jun B, or TNF receptor 1B, but not mutated GRE sequences, into the 3'UTR of a beta-globin transcript conferred instability on the otherwise stable beta-globin transcript. CUG-binding protein 1 (CUGBP1) was identified as the major GRE-binding activity in cytoplasmic extracts from primary human T cells based on supershift and immunoprecipitation assays. siRNA-mediated knockdown of CUGBP1 in HeLa cells caused stabilization of GRE-containing transcripts, suggesting that CUGBP1 is a mediator of GRE-dependent mRNA decay. Overall, our results suggest that the GRE mediates coordinated mRNA decay by binding to CUGBP1.
Vlasova
Irina A
IA
Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN 55455, USA.
Tahoe
Nuzha M
NM
Fan
Danhua
D
Larsson
Ola
O
Rattenbacher
Bernd
B
Sternjohn
Julius R
JR
Vasdewani
Jayprakash
J
Karypis
George
G
Reilly
Cavan S
CS
Bitterman
Peter B
PB
Bohjanen
Paul R
PR
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D000067879:CELF1 Protein; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D020413:3' Untranslated Regions; D000067879:CELF1 Protein; C102843:CELF1 protein, human; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D018124:Receptors, Tumor Necrosis Factor; D005914:Globins