PMID- 9819424
OWN - NLM
STAT- MEDLINE
DCOM- 19981224
LR  - 20240213
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 18
IP  - 12
DP  - 1998 Dec
TI  - Highly conserved RNA sequences that are sensors of environmental stress.
PG  - 7371-82
AB  - The putative function of highly conserved regions (HCRs) within 3' untranslated 
      regions (3'UTRs) as regulatory RNA sequences was efficiently and quantitatively 
      assessed by using modular retroviral vectors. This strategy led to the 
      identification of HCRs that alter gene expression in response to oxidative or 
      mitogenic stress. Databases were screened for UTR sequences of >100 nucleotides 
      that had retained 70% identity over more than 300 million years of evolution. The 
      effects of 10 such HCRs on a standard reporter mRNA or protein were studied. To 
      this end, we developed a modular retroviral vector that can allow for a direct 
      comparison of the effects of different HCRs on gene expression independent of 
      their gene-intrinsic 5'UTR, promoter, protein coding region, or poly(A) sequence. 
      Five of the HCRs tested decreased mRNA steady-state levels 2- to 10-fold relative 
      to controls, presumably by altering mRNA stability. One HCR increased 
      translation, and one decreased translation. Elevated mitogen levels caused four 
      HCRs to increase protein levels twofold. One HCR increased protein levels 
      fourfold in response to hypoxia. Although nonconserved UTR sequences may also 
      have a role, these results provide evidence that sequences that are highly 
      conserved during evolution are good candidates for RNA motifs with 
      posttranscriptional regulatory functions in gene expression.
FAU - Spicher, A
AU  - Spicher A
AD  - Department of Molecular Pharmacology, Department of Radiation Oncology, Stanford 
      University School of Medicine, Stanford, California 94305-5332, USA.
FAU - Guicherit, O M
AU  - Guicherit OM
FAU - Duret, L
AU  - Duret L
FAU - Aslanian, A
AU  - Aslanian A
FAU - Sanjines, E M
AU  - Sanjines EM
FAU - Denko, N C
AU  - Denko NC
FAU - Giaccia, A J
AU  - Giaccia AJ
FAU - Blau, H M
AU  - Blau HM
LA  - eng
GR  - R37 AG009521/AG/NIA NIH HHS/United States
GR  - CA73832/CA/NCI NIH HHS/United States
GR  - R01 AG009521/AG/NIA NIH HHS/United States
GR  - 5T32CA09302/CA/NCI NIH HHS/United States
GR  - R01 HD018179/HD/NICHD NIH HHS/United States
GR  - AG09521/AG/NIA NIH HHS/United States
GR  - T32 CA009302/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Mitogens)
RN  - 0 (RNA, Messenger)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - 3' Untranslated Regions/*genetics
MH  - Animals
MH  - Biological Evolution
MH  - Cell Line
MH  - Conserved Sequence/*genetics
MH  - Flow Cytometry
MH  - Gene Expression Regulation/genetics
MH  - Genes, Regulator/genetics
MH  - Genes, Reporter/genetics
MH  - Hypoxia/genetics
MH  - Mice
MH  - Mitogens/pharmacology
MH  - Protein Biosynthesis
MH  - RNA/*genetics
MH  - RNA, Messenger/genetics
MH  - Retroviridae/genetics
MH  - *Stress, Physiological
PMC - PMC109319
EDAT- 1998/11/20 00:00
MHDA- 1998/11/20 00:01
PMCR- 1998/12/01
CRDT- 1998/11/20 00:00
PHST- 1998/11/20 00:00 [pubmed]
PHST- 1998/11/20 00:01 [medline]
PHST- 1998/11/20 00:00 [entrez]
PHST- 1998/12/01 00:00 [pmc-release]
AID - 0861 [pii]
AID - 10.1128/MCB.18.12.7371 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1998 Dec;18(12):7371-82. doi: 10.1128/MCB.18.12.7371.