|
|
 Previous Article | Table of Contents | Next Article 
Number and location of AUUUA motifs: role in regulating transiently
expressed RNAs
M Akashi, G Shaw, M Hachiya, E Elstner, G Suzuki and P Koeffler
Division of Radiation Health, National Institute of Radiological Sciences,
Chiba, Japan.
Many RNAs coding for either cytokines or oncogenes are unstable and have a
short half-life (t1/2). The AUUUA motif is a highly conserved sequence and
is repeated three or more times in the 3' untranslated region (3'UTR) of
RNAs encoding many of these short-lived cytokines and oncogenes. These
sequences can confer instability. In this study, we investigated the role
of number and location of AUUUA motifs in stabilization of RNA. We
introduced 1xATTTA, 2xATTTA, ATTTTTTTA (second adenosine of 2xATTTA was
substituted with a thymidine), 3xATTTA, 5xATTTA, 7xATTTA [AT-rich sequence
from granulocyte-macrophage colony- stimulating factor [GM-CSF] gene
(AT-62)], and GC-62 (GC sequences were substituted for ATTTA sequences in
the 7xATTTA) into the 3'UTR of rabbit beta-globin (R beta G) gene. This
construct also contained the neomycin-resistance gene. These expression
vectors were transfected into human lung fibroblasts (W138), which
constitutively expressed low levels of GM-CSF mRNA. Stable transfectants
were selected by growth in G418. Northern blot analysis of actinomycin
D-treated, stably transfected cells demonstrated that the number of AUUUA
sequences correlated with rapidity of turnover of the chimeric R beta G
mRNA. The rank order of stability was GC-62 = 1xATTTA = 2xATTTA (no RNA
decay at 4 hours) > 3xATTTA = 5xATTTA (t1/2, 4 hours) > 7xATTTA
(t1/2, 2 hours). Stability of mRNA of R beta G also was reduced (t1/2, 2 to
4 hours) when AT-62 was introduced into the second exon of R beta G gene.
In these same cells, the t1/2 of GM-CSF RNA was approximately 10 to 15
minutes, suggesting that the AUUUA motifs cannot alone account for the
rapid degradation of this cytokine mRNA. Phorbol diesters, including 12-
0-tetradecanoyl phorbol 13-acetate (TPA), stabilize a variety of
transiently expressed RNAs, including GM-CSF RNA. We found that TPA
markedly increased (> 30-fold) the accumulation of GM-CSF RNA. In
contrast, TPA was unable to stimulate the levels of the chimeric R beta G
when either 1x, 2x, 3x, or 5xATTTA motifs were fused to 3'UTR, or when
either AT-62 or GC-62 control sequences were fused to the second exon. The
chimeric beta-globin construct with either AT-62 or ATTTTTTTA in the 3'UTR
had only an approximately twofold to threefold increase in
accumulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 83,
Issue 11,
pp. 3182-3187,
06/01/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Akoum, C. N. Metz, and M. Morin
Marked Increase in Macrophage Migration Inhibitory Factor Synthesis and Secretion in Human Endometrial Cells in Response to Human Chorionic Gonadotropin Hormone
J. Clin. Endocrinol. Metab.,
May 1, 2005;
90(5):
2904 - 2910.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Demasi, L. G. Cleland, R. J. Cook-Johnson, G. E. Caughey, and M. J. James
Effects of Hypoxia on Monocyte Inflammatory Mediator Production: DISSOCIATION BETWEEN CHANGES IN CYCLOOXYGENASE-2 EXPRESSION AND EICOSANOID SYNTHESIS
J. Biol. Chem.,
October 3, 2003;
278(40):
38607 - 38616.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J M M Tan, E P C Tock, and V T K Chow
The novel human MOST-1 (C8orf17) gene exhibits tissue specific expression, maps to chromosome 8q24.2, and is overexpressed/amplified in high grade cancers of the breast and prostate
Mol. Pathol.,
April 1, 2003;
56(2):
109 - 115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. G. Haddad and E. Ma
Book Review: Neuronal Tolerance to O2 Deprivation in Drosophila: Novel Approaches Using Genetic Models
Neuroscientist,
December 1, 2001;
7(6):
538 - 550.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Bakheet, M. Frevel, B. R. G. Williams, W. Greer, and K. S. A. Khabar
ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins
Nucleic Acids Res.,
January 1, 2001;
29(1):
246 - 254.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bergmann, P. J. Barnes, and R. Newton
Molecular Regulation of Granulocyte Macrophage Colony-Stimulating Factor in Human Lung Epithelial Cells by Interleukin (IL)-1beta , IL-4, and IL-13 Involves Both Transcriptional and Post-Transcriptional Mechanisms
Am. J. Respir. Cell Mol. Biol.,
May 1, 2000;
22(5):
582 - 589.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. Chrysis and L. E. Underwood
Regulation of Components of the Ubiquitin System by Insulin-Like Growth Factor I and Growth Hormone in Skeletal Muscle of Rats Made Catabolic with Dexamethasone
Endocrinology,
December 1, 1999;
140(12):
5635 - 5641.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. S. Buzby, G. Brewer, and D. J. Nugent
Developmental Regulation of RNA Transcript Destabilization by A + U-rich Elements is AUF1-dependent
J. Biol. Chem.,
November 26, 1999;
274(48):
33973 - 33978.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Shepard and J. L. Rae
Electrically silent potassium channel subunits from human lens epithelium
Am J Physiol Cell Physiol,
September 1, 1999;
277(3):
C412 - C424.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ribadeau-Dumas, M. Brady, S. Y Boateng, K. Schwartz, and K. R Boheler
Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) gene products are regulated post-transcriptionally during rat cardiac development
Cardiovasc Res,
August 1, 1999;
43(2):
426 - 436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kosaki, J. Ando, R. Korenaga, T. Kurokawa, and A. Kamiya
Fluid Shear Stress Increases the Production of Granulocyte-Macrophage Colony-Stimulating Factor by Endothelial Cells via mRNA Stabilization
Circ. Res.,
April 20, 1998;
82(7):
794 - 802.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Burke, H. Wang, W. Hide, and D. B. Davison
Alternative Gene Form Discovery and Candidate Gene Selection from Gene Indexing Projects
Genome Res.,
March 1, 1998;
8(3):
276 - 290.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
F. G. Rolfe, J. E. Valentine, and W. A. Sewell
Cyclosporin A and FK506 Reduce Interleukin-5 mRNA Abundance by Inhibiting Gene Transcription
Am. J. Respir. Cell Mol. Biol.,
August 1, 1997;
17(2):
243 - 250.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
B. G. Tholanikunnel and C. C. Malbon
A 20-Nucleotide (A+U)-rich Element of beta 2-Adrenergic Receptor (beta 2AR) mRNA Mediates Binding to beta 2AR-binding Protein and Is Obligate for Agonist-induced Destabilization of Receptor mRNA
J. Biol. Chem.,
April 25, 1997;
272(17):
11471 - 11478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Y. Brown, C. A. Lagnado, and G. J. Goodall
A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements
PNAS,
November 26, 1996;
93(24):
13721 - 13725.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. E. Rajagopalan and J. S. Malter
Turnover and Translation of in Vitro Synthesized Messenger RNAs in Transfected, Normal Cells
J. Biol. Chem.,
August 16, 1996;
271(33):
19871 - 19876.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Wymore, D. Negulescu, K. Kinoshita, K. Kalman, J. Aiyar, G. A. Gutman, and K. G. Chandy
Characterization of the Transcription Unit of Mouse Kv1.4, a Voltage-gated Potassium Channel Gene
J. Biol. Chem.,
June 28, 1996;
271(26):
15629 - 15634.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. DeMaria and G. Brewer
AUF1 Binding Affinity to A+U-rich Elements Correlates with Rapid mRNA Degradation
J. Biol. Chem.,
May 24, 1996;
271(21):
12179 - 12184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Akashi, M. Hachiya, R. L. Paquette, Y. Osawa, S. Shimizu, and G. Suzuki
Irradiation Increases Manganese Superoxide Dismutase mRNA Levels in Human Fibroblasts
J. Biol. Chem.,
June 30, 1995;
270(26):
15864 - 15869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. P. Levy, N. S. Levy, S. Wegner, and M. A. Goldberg
Transcriptional Regulation of the Rat Vascular Endothelial Growth Factor Gene by Hypoxia
J. Biol. Chem.,
June 2, 1995;
270(22):
13333 - 13340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ghanshani, H. Wulff, M. J. Miller, H. Rohm, A. Neben, G. A. Gutman, M. D. Cahalan, and K. G. Chandy
Up-regulation of the IKCa1 Potassium Channel during T-cell Activation. MOLECULAR MECHANISM AND FUNCTIONAL CONSEQUENCES
J. Biol. Chem.,
November 17, 2000;
275(47):
37137 - 37149.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
