The tumor necrosis factor-alpha AU-rich element inhibits the stable association of the 40S ribosomal subunit with RNA transcripts.
Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine that is central to normal immune responses as well as autoimmune inflammatory diseases. The production of TNF-alpha protein is thus tightly regulated at multiple levels. Translational control is one of the means by which TNF-alpha production is repressed in unstimulated cells. To examine the mechanism by which the translation of TNF-alpha mRNA transcripts is repressed, we have used an in vitro translation system. The AU-rich element (ARE) in the 3' UTR of TNF-alpha transcripts was sufficient to confer translational repression. This effect was observed using transcripts containing a 5' m(7)G cap but not uncapped transcripts, and was independent of a poly(A) tail. Sucrose gradient analysis revealed that ARE-containing transcripts were present at relatively lower amounts in 80S-associated fractions and higher amounts in non-ribosome-bound RNA fractions, with no accumulation of 48S-associated transcripts. ARE-mediated translational repression was competitively inhibited by ARE-containing transcripts. These data indicate that a TNF-alpha ARE-binding trans-acting factor(s) inhibits the association of the 43S complex with RNA transcripts.
Wax
Stephen D
SD
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nakamura
Hideki
H
Anderson
Paul J
PJ
D001483:Base Sequence; D005786:Gene Expression Regulation / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D021122:Protein Subunits; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D021122:Protein Subunits; D012097:Repressor Proteins; D012269:Ribosomal Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha