PMID- 9592171
OWN - NLM
STAT- MEDLINE
DCOM- 19980720
LR  - 20190501
IS  - 0305-1048 (Print)
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Linking)
VI  - 26
IP  - 11
DP  - 1998 Jun 1
TI  - Characterization of the RNA binding proteins forming complexes with a novel 
      putative regulatory region in the 3'-UTR of TNF-alpha mRNA.
PG  - 2803-12
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine regulator of an early 
      immune response and the central mediator of deleterious effects of systemic 
      inflammatory response syndrome. High production of TNF-alpha by macrophages 
      requires two signals: the first signal induces transcription, while the second 
      signal releases the translational repression of TNF-alpha mRNA. The translational 
      control of TNF-alpha expression is conferred by sequences in the 3'-untranslated 
      region (3'-UTR) of its mRNA. Previously, we have characterized protein complexes 
      binding to the main AU-rich region in the 3'-UTR of murine TNF-alpha mRNA. Here 
      we describe a second protein binding region which is located 147 bases downstream 
      of the first region and interacts with at least seven distinct protein species 
      present in murine macrophages. The second protein binding motif contains a single 
      AUAUUUAU sequence motif; a mutation of this sequence to AUAGGUAU abrogates the 
      binding of proteins. Some of the macrophage proteins mutually compete for the 
      binding to both regions, while others seem to be region specific. The existence 
      of the two protein binding domains explains the previously published data 
      addressing the translatibility of a reporter gene linked to various deletion 
      mutants of the TNF-alpha 3'-UTR. Both the sequence and position of the two 
      putative protein binding regions are highly conserved across species, indicating 
      their important role in the regulation of translational repression and 
      inducibility of TNF-alpha synthesis.
FAU - Hel, Z
AU  - Hel Z
AD  - McGill Centre for the Study of Host Resistance, McGill University, Montreal 
      General Hospital Research Institute, Montreal, Quebec H3G 1A4, Canada.
FAU - Di Marco, S
AU  - Di Marco S
FAU - Radzioch, D
AU  - Radzioch D
LA  - eng
SI  - GENBANK/A19163
SI  - GENBANK/D00475
SI  - GENBANK/J00370
SI  - GENBANK/M11731
SI  - GENBANK/M12845
SI  - GENBANK/M15131
SI  - GENBANK/M32599
SI  - GENBANK/X01394
SI  - GENBANK/X14828
SI  - GENBANK/X56321
SI  - GENBANK/Z14137
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (RNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - JAC85A2161 (Adenine)
RN  - WHI7HQ7H85 (Uridine)
SB  - IM
MH  - Adenine
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Line
MH  - Conserved Sequence
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Protein Biosynthesis
MH  - RNA, Complementary
MH  - RNA, Messenger/*metabolism
MH  - RNA-Binding Proteins/*metabolism
MH  - Rabbits
MH  - Rats
MH  - *Regulatory Sequences, Nucleic Acid
MH  - Sequence Homology, Nucleic Acid
MH  - Species Specificity
MH  - Tumor Necrosis Factor-alpha/*genetics
MH  - Uridine
PMC - PMC147622
EDAT- 1998/05/21 00:00
MHDA- 1998/05/21 00:01
PMCR- 1998/06/01
CRDT- 1998/05/21 00:00
PHST- 1998/05/21 00:00 [pubmed]
PHST- 1998/05/21 00:01 [medline]
PHST- 1998/05/21 00:00 [entrez]
PHST- 1998/06/01 00:00 [pmc-release]
AID - gkb443 [pii]
AID - 10.1093/nar/26.11.2803 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 1998 Jun 1;26(11):2803-12. doi: 10.1093/nar/26.11.2803.