| 研究生: |
徐千惠 Hsu, Chien-Hui |
|---|---|
| 論文名稱: |
FGF9基因3’UTR序列對調控FGF9蛋白質表現之研究 The post-transcriptional regulation of human FGF9 3’ untranslated region (3’UTR) on FGF9 protein expression |
| 指導教授: |
孫孝芳
Sun, Hsiao-Fang Sunny |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 分子醫學研究所 Institute of Molecular Medicine |
| 論文出版年: | 2005 |
| 畢業學年度: | 93 |
| 語文別: | 英文 |
| 論文頁數: | 83 |
| 中文關鍵詞: | 第九纖維母細胞生長因子 、三端非轉譯序列 |
| 外文關鍵詞: | 3'UTR, ARE, FGF9, MS |
| 相關次數: | 點閱:110 下載:3 |
| 分享至: |
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細胞中的後轉錄調控是經由調節核醣核酸穩定度、轉譯效率、訊息核醣核酸的運輸與位移以及多聚腺核苷酸的選擇與長度來調節基因的表現量。主要是藉由非轉譯序列和其特定之調控蛋白交互作用來調控。其中,三端非轉譯的區域已在先前的研究中被指出,是決定發育時期細胞不同蛋白質表現分佈的重要調控序列。第九纖維母細胞生長因子在先前的動物研究中被發現是一個對胚胎發育、器官形成、性別發育和維持生命機能都十分重要的內分泌物質;然而目前對於人類第九纖維母細胞生長因子基因調控的研究所知有限。本實驗室先前之研究指出此基因的三端非轉譯序列上之微衛星序列具有調控基因表現的能力;進一步的生物資訊分析發現,此區域有富含腺核苷酸及尿核苷酸的序列存在,可能參與基因調控,並在表達序列標籤資料庫中,亦發現此基因有數種不同長度的三端非轉譯序列。這些結果都指出人類第九纖維母細胞生長因子的三端非轉譯序列研究之重要性。因此,這個實驗的主要目的在於找出此區域中具調控功能的序列及相互作用之蛋白質。我們利用快速放大基因末端片段的方法,發現在人類胚胎腎細胞株(HEK293)中有五種不同的三端非轉譯序列存在。此五種不同的片段包含微衛星序列及富含腺核苷酸及尿核苷酸序列之各種組合。進而利用冷光報導基因系統來研究此兩種調控序列和不同的三端非轉譯片段對此生長因子表現的調控,實驗結果顯示此兩種調控序列的突變皆會增加蛋白質的表現量,而不同的三端非轉譯片段也有不同的調控能力。進一步的實驗也發現,此兩種調控序列是經由與特定調控蛋白的結合來增加核醣核酸的不穩定度。綜合以上結果顯示,在人類第九纖維母細胞生長因子的三端非轉譯序列上,微衛星序列及富含腺核苷酸及尿核苷酸序列,可經由讓核醣核酸較不穩定的負調控方式來改變人類第九纖維母細胞生長因子在細胞中的表現程度。
Post-transcriptional control, which includes determining transcript stability, level of translation, mRNA targeting, poly (A) shortening and alternative polyadenylation, has been shown to regulate protein expression via interaction of untranslated regions (5’ and 3’UTR) with regulatory proteins. Recent studies reveal the power of 3’UTR in controlling cell–fate determination, location and timing of cell division, and shaping the expression pattern during development. Fibroblast growth factor 9 (FGF9) is an autocrine/paracrine growth factor that plays important roles in embryonic development, organ development, sexual development and physiologic maintenances. Limited studies have reported the expression control of human FGF9. Our previous study has demonstrated the microsatellite (MS) motif of FGF9 3’UTR can influence gene expression in a reporter gene system. Additional sequence analysis using bioinformatics tools suggested the AU-rich element (ARE) of FGF9 3’UTR may also participate in regulating FGF9 mRNAs. Furthermore, information from searching EST database showed several FGF9 transcripts with different length in 3’UTR. These data suggested the potential regulatory role of FGF9 3’UTR on FGF9 protein expression. This study aims to identify all possible functional cis-elements of FGF9 3’UTR and its associated proteins. We have identified five FGF9 transcripts with different lengths in 3’end by 3’RACE in HEK293 cells. The varied lengths of 614-, 549-, 194-, 73-, and 50-bp from the stop codon of FGF9 transcript are containing both MS and ARE motifs, MS motif only, or none of the motifs. The role of each element and varied FGF9 transcripts in regulating FGF9 protein expression is investigated using luciferase assay. The data showed either a point mutation within the AUUUA motif or deletion of FGF9 3’UTR MS motif significantly increased reporter gene activity in HEK293 cells, besides; the different FGF9 transcripts have various expression level of reporter gene. Additional mRNA turnover and RNA-protein interaction studies suggested both ARE and MS motif of FGF9 3’UTR may destabilize FGF9 mRNA through the interactions and RNA-binding proteins. In conclusion, results from this study indicate ARE and MS motifs of FGF9 3’UTR can modulate FGF9 protein expression by destabilizing FGF9 mRNA stability.
Aharon T, Schneider RJ (1993) Selective destabilization of short-lived mRNAs with the granulocyte-macrophage colony-stimulating factor AU-rich 3' noncoding region is mediated by a cotranslational mechanism. Mol Cell Biol 13:1971-1980
Ambrosino C, Mace G, Galban S, Fritsch C, Vintersten K, Black E, Gorospe M, Nebreda AR (2003) Negative feedback regulation of MKK6 mRNA stability by p38alpha mitogen-activated protein kinase. Mol Cell Biol 23:370-381
Anderson P (2000) Post-transcriptional regulation of tumour necrosis factor alpha production. Ann Rheum Dis 59 Suppl 1:i3-5
Bakheet T, Frevel M, Williams BR, Greer W, Khabar KS (2001) ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins. Nucleic Acids Res 29:246-254
Beelman CA, Parker R (1995) Degradation of mRNA in eukaryotes. Cell 81:179-183
Bevilacqua A, Ceriani MC, Capaccioli S, Nicolin A (2003) Post-transcriptional regulation of gene expression by degradation of messenger RNAs. J Cell Physiol 195:356-372
Bohjanen PR, Petryniak B, June CH, Thompson CB, Lindsten T (1991) An inducible cytoplasmic factor (AU-B) binds selectively to AUUUA multimers in the 3' untranslated region of lymphokine mRNA. Mol Cell Biol 11:3288-3295
Bohjanen PR, Petryniak B, June CH, Thompson CB, Lindsten T (1992) AU RNA-binding factors differ in their binding specificities and affinities. J Biol Chem 267:6302-6309
Borrmann L, Seebeck B, Rogalla P, Bullerdiek J (2003) Human HMGA2 promoter is coregulated by a polymorphic dinucleotide (TC)-repeat. Oncogene 22:756-760
Brewer G (1991) An A + U-rich element RNA-binding factor regulates c-myc mRNA stability in vitro. Mol Cell Biol 11:2460-2466
Brown CY, Lagnado CA, Goodall GJ (1996) A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements. Proc Natl Acad Sci U S A 93:13721-13725
Caput D, Beutler B, Hartog K, Thayer R, Brown-Shimer S, Cerami A (1986) Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A 83:1670-1674
Chen CY, Gherzi R, Ong SE, Chan EL, Raijmakers R, Pruijn GJ, Stoecklin G, Moroni C, Mann M, Karin M (2001) AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107:451-464
Chen CY, Shyu AB (1994) Selective degradation of early-response-gene mRNAs: functional analyses of sequence features of the AU-rich elements. Mol Cell Biol 14:8471-8482
Chen CY, Shyu AB (1995) AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem Sci 20:465-470
Chen CY, Xu N, Shyu AB (1995) mRNA decay mediated by two distinct AU-rich elements from c-fos and granulocyte-macrophage colony-stimulating factor transcripts: different deadenylation kinetics and uncoupling from translation. Mol Cell Biol 15:5777-5788
Cleveland DW, Yen TJ (1989) Multiple determinants of eukaryotic mRNA stability. New Biol 1:121-126
Cohen RI, Chandross KJ (2000) Fibroblast growth factor-9 modulates the expression of myelin related proteins and multiple fibroblast growth factor receptors in developing oligodendrocytes. J Neurosci Res 61:273-287
Colvin JS, Green RP, Schmahl J, Capel B, Ornitz DM (2001) Male-to-female sex reversal in mice lacking fibroblast growth factor 9. Cell 104:875-889
Cougot N, Babajko S, Seraphin B (2004) Cytoplasmic foci are sites of mRNA decay in human cells. J Cell Biol 165:31-40
Curatola AM, Nadal MS, Schneider RJ (1995) Rapid degradation of AU-rich element (ARE) mRNAs is activated by ribosome transit and blocked by secondary structure at any position 5' to the ARE. Mol Cell Biol 15:6331-6340
DeMaria CT, Brewer G (1996) AUF1 binding affinity to A+U-rich elements correlates with rapid mRNA degradation. J Biol Chem 271:12179-12184
Dominski Z, Zheng LX, Sanchez R, Marzluff WF (1999) Stem-loop binding protein facilitates 3'-end formation by stabilizing U7 snRNP binding to histone pre-mRNA. Mol Cell Biol 19:3561-3570
Fan XC, Myer VE, Steitz JA (1997) AU-rich elements target small nuclear RNAs as well as mRNAs for rapid degradation. Genes Dev 11:2557-2568
Fan XC, Steitz JA (1998) Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. Embo J 17:3448-3460
Farhana L, Boyanapalli M, Tschang SH, Sun RJ, Hsu CK, Zhang YX, Fontana JA, Rishi AK (2000) Okadaic acid-mediated induction of the c-fos gene in estrogen receptor-negative human breast carcinoma cells utilized, in part, posttranscriptional mechanisms involving adenosine-uridine-rich elements. Cell Growth Differ 11:541-550
Fritz DT, Ford LP, Wilusz J (2000) An in vitro assay to study regulated mRNA stability. Sci STKE 2000:PL1
Gao M, Wilusz CJ, Peltz SW, Wilusz J (2001) A novel mRNA-decapping activity in HeLa cytoplasmic extracts is regulated by AU-rich elements. Embo J 20:1134-1143
Garces A, Nishimune H, Philippe JM, Pettmann B, deLapeyriere O (2000) FGF9: a motoneuron survival factor expressed by medial thoracic and sacral motoneurons. J Neurosci Res 60:1-9
Good PJ (1995) A conserved family of elav-like genes in vertebrates. Proc Natl Acad Sci U S A 92:4557-4561
Gorlach M, Burd CG, Dreyfuss G (1994) The mRNA poly(A)-binding protein: localization, abundance, and RNA-binding specificity. Exp Cell Res 211:400-407
Gorospe M, Baglioni C (1994) Degradation of unstable interleukin-1 alpha mRNA in a rabbit reticulocyte cell-free system. Localization of an instability determinant to a cluster of AUUUA motifs. J Biol Chem 269:11845-11851
Grzybowska EA, Wilczynska A, Siedlecki JA (2001) Regulatory functions of 3'UTRs. Biochem Biophys Res Commun 288:291-295
Guhaniyogi J, Brewer G (2001) Regulation of mRNA stability in mammalian cells. Gene 265:11-23
Hamilton BJ, Nagy E, Malter JS, Arrick BA, Rigby WF (1993) Association of heterogeneous nuclear ribonucleoprotein A1 and C proteins with reiterated AUUUA sequences. J Biol Chem 268:8881-8887
Henics T (1999) Microfilament-dependent modulation of cytoplasmic protein binding to TNFalpha mRNA AU-rich instability element in human lymphoid cells. Cell Biol Int 23:561-570
Holcik M, Sonenberg N, Korneluk RG (2000) Internal ribosome initiation of translation and the control of cell death. Trends Genet 16:469-473
Jacobson A, Peltz SW (1996) Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells. Annu Rev Biochem 65:693-739
Kettunen P, Thesleff I (1998) Expression and function of FGFs-4, -8, and -9 suggest functional redundancy and repetitive use as epithelial signals during tooth morphogenesis. Dev Dyn 211:256-268
Klein RD, Maliner-Jongewaard MS, Udayakumar TS, Boyd JL, Nagle RB, Bowden GT (1999) Promatrilysin expression is induced by fibroblast growth factors in the prostatic carcinoma cell line LNCaP but not in normal primary prostate epithelial cells. Prostate 41:215-223
Lagnado CA, Brown CY, Goodall GJ (1994) AUUUA is not sufficient to promote poly(A) shortening and degradation of an mRNA: the functional sequence within AU-rich elements may be UUAUUUA(U/A)(U/A). Mol Cell Biol 14:7984-7995
Laroia G, Cuesta R, Brewer G, Schneider RJ (1999) Control of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 284:499-502
Levine TD, Gao F, King PH, Andrews LG, Keene JD (1993) Hel-N1: an autoimmune RNA-binding protein with specificity for 3' uridylate-rich untranslated regions of growth factor mRNAs. Mol Cell Biol 13:3494-3504
Lovicu FJ, Overbeek PA (1998) Overlapping effects of different members of the FGF family on lens fiber differentiation in transgenic mice. Development 125:3365-3377
Ma WJ, Cheng S, Campbell C, Wright A, Furneaux H (1996) Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein. J Biol Chem 271:8144-8151
Malter JS, Hong Y (1991) A redox switch and phosphorylation are involved in the post-translational up-regulation of the adenosine-uridine binding factor by phorbol ester and ionophore. J Biol Chem 266:3167-3171
Mangus DA, Evans MC, Jacobson A (2003) Poly(A)-binding proteins: multifunctional scaffolds for the post-transcriptional control of gene expression. Genome Biol 4:223
Mangus DA, Jacobson A (1999) Linking mRNA turnover and translation: assessing the polyribosomal association of mRNA decay factors and degradative intermediates. Methods 17:28-37
Matsumoto-Yoshitomi S, Kuroshima K, Nomura C, Habashita J, Kurokawa T (1996) Construction of a sensitive enzyme immunoassay for human fibroblast growth factor 9. Hybridoma 15:299-305
Mattei MG, Penault-Llorca F, Coulier F, Birnbaum D (1995) The human FGF9 gene maps to chromosomal region 13q11-q12. Genomics 29:811-812
Mawji IA, Robb GB, Tai SC, Marsden PA (2004) Role of the 3'-untranslated region of human endothelin-1 in vascular endothelial cells. Contribution to transcript lability and the cellular heat shock response. J Biol Chem 279:8655-8667
McGowan KM, Police S, Winslow JB, Pekala PH (1997) Tumor necrosis factor-alpha regulation of glucose transporter (GLUT1) mRNA turnover. Contribution of the 3'-untranslated region of the GLUT1 message. J Biol Chem 272:1331-1337
Mignone F, Gissi C, Liuni S, Pesole G (2002) Untranslated regions of mRNAs. Genome Biol 3:REVIEWS0004
Mignone F, Grillo G, Licciulli F, Iacono M, Liuni S, Kersey PJ, Duarte J, Saccone C, Pesole G (2005) UTRdb and UTRsite: a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs. Nucleic Acids Res 33:D141-146
Milanesi L, Muselli M, Arrigo P (1996) Hamming-Clustering method for signals prediction in 5' and 3' regions of eukaryotic genes. Comput Appl Biosci 12:399-404
Miyamoto M, Naruo K, Seko C, Matsumoto S, Kondo T, Kurokawa T (1993) Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property. Mol Cell Biol 13:4251-4259
Nabors LB, Suswam E, Huang Y, Yang X, Johnson MJ, King PH (2003) Tumor necrosis factor alpha induces angiogenic factor up-regulation in malignant glioma cells: a role for RNA stabilization and HuR. Cancer Res 63:4181-4187
Nagy E, Rigby WF (1995) Glyceraldehyde-3-phosphate dehydrogenase selectively binds AU-rich RNA in the NAD(+)-binding region (Rossmann fold). J Biol Chem 270:2755-2763
Nakagawa J, Waldner H, Meyer-Monard S, Hofsteenge J, Jeno P, Moroni C (1995) AUH, a gene encoding an AU-specific RNA binding protein with intrinsic enoyl-CoA hydratase activity. Proc Natl Acad Sci U S A 92:2051-2055
Nakamura S, Arima K, Haga S, Aizawa T, Motoi Y, Otsuka M, Ueki A, Ikeda K (1998) Fibroblast growth factor (FGF)-9 immunoreactivity in senile plaques. Brain Res 814:222-225
Nakamura S, Todo T, Haga S, Aizawa T, Motoi Y, Ueki A, Kurokawa T, Ikeda K (1997) Motor neurons in human and rat spinal cord synthesize fibroblast growth factor-9. Neurosci Lett 221:181-184
Nakamura S, Todo T, Motoi Y, Haga S, Aizawa T, Ueki A, Ikeda K (1999) Glial expression of fibroblast growth factor-9 in rat central nervous system. Glia 28:53-65
Naruo K, Seko C, Kuroshima K, Matsutani E, Sasada R, Kondo T, Kurokawa T (1993) Novel secretory heparin-binding factors from human glioma cells (glia-activating factors) involved in glial cell growth. Purification and biological properties. J Biol Chem 268:2857-2864
Okladnova O, Syagailo YV, Tranitz M, Riederer P, Stober G, Mossner R, Lesch KP (1999) Functional characterization of the human PAX3 gene regulatory region. Genomics 57:110-119
Okladnova O, Syagailo YV, Tranitz M, Stober G, Riederer P, Mossner R, Lesch KP (1998) A promoter-associated polymorphic repeat modulates PAX-6 expression in human brain. Biochem Biophys Res Commun 248:402-405
Penault-Llorca F, Bertucci F, Adelaide J, Parc P, Coulier F, Jacquemier J, Birnbaum D, deLapeyriere O (1995) Expression of FGF and FGF receptor genes in human breast cancer. Int J Cancer 61:170-176
Pesole G, Liuni S, Grillo G, Licciulli F, Mignone F, Gissi C, Saccone C (2002) UTRdb and UTRsite: specialized databases of sequences and functional elements of 5' and 3' untranslated regions of eukaryotic mRNAs. Update 2002. Nucleic Acids Res 30:335-340
Peters DG, Kassam A, St Jean PL, Yonas H, Ferrell RE (1999) Functional polymorphism in the matrix metalloproteinase-9 promoter as a potential risk factor for intracranial aneurysm. Stroke 30:2612-2616
Piecyk M, Wax S, Beck AR, Kedersha N, Gupta M, Maritim B, Chen S, Gueydan C, Kruys V, Streuli M, Anderson P (2000) TIA-1 is a translational silencer that selectively regulates the expression of TNF-alpha. Embo J 19:4154-4163
Posch M, Sutterluety H, Skern T, Seiser C (1999) Characterization of the translation-dependent step during iron-regulated decay of transferrin receptor mRNA. J Biol Chem 274:16611-16618
Powers CJ, McLeskey SW, Wellstein A (2000) Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer 7:165-197
Robinson D, Hasharoni A, Evron Z, Segal M, Nevo Z (2000) Synovial chondromatosis: the possible role of FGF 9 and FGF receptor 3 in its pathology. Int J Exp Pathol 81:183-189
Rouault T, Klausner R (1997) Regulation of iron metabolism in eukaryotes. Curr Top Cell Regul 35:1-19
Schmahl J, Kim Y, Colvin JS, Ornitz DM, Capel B (2004) Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination. Development 131:3627-3636
Searle S, Blackwell JM (1999) Evidence for a functional repeat polymorphism in the promoter of the human NRAMP1 gene that correlates with autoimmune versus infectious disease susceptibility. J Med Genet 36:295-299
Seo M, Noguchi K (1995) Retinoic acid induces gene expression of fibroblast growth factor-9 during induction of neuronal differentiation of mouse embryonal carcinoma P19 cells. FEBS Lett 370:231-235
Shaw G, Kamen R (1986) A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46:659-667
Staton JM, Leedman PJ (1998) Posttranscriptional regulation of thyrotropin beta-subunit messenger ribonucleic acid by thyroid hormone in murine thyrotrope tumor cells: a conserved mechanism across species. Endocrinology 139:1093-1100
Staton JM, Thomson AM, Leedman PJ (2000) Hormonal regulation of mRNA stability and RNA-protein interactions in the pituitary. J Mol Endocrinol 25:17-34
Stoecklin G, Lu M, Rattenbacher B, Moroni C (2003) A constitutive decay element promotes tumor necrosis factor alpha mRNA degradation via an AU-rich element-independent pathway. Mol Cell Biol 23:3506-3515
Sweeney R, Fan Q, Yao MC (1996) Antisense ribosomes: rRNA as a vehicle for antisense RNAs. Proc Natl Acad Sci U S A 93:8518-8523
Tagashira S, Ozaki K, Ohta M, Itoh N (1995) Localization of fibroblast growth factor-9 mRNA in the rat brain. Brain Res Mol Brain Res 30:233-241
Taylor GA, Thompson MJ, Lai WS, Blackshear PJ (1996) Mitogens stimulate the rapid nuclear to cytosolic translocation of tristetraprolin, a potential zinc-finger transcription factor. Mol Endocrinol 10:140-146
Thomson AM, Rogers JT, Leedman PJ (1999) Iron-regulatory proteins, iron-responsive elements and ferritin mRNA translation. Int J Biochem Cell Biol 31:1139-1152
Timchenko LT (1999) Myotonic dystrophy: the role of RNA CUG triplet repeats. Am J Hum Genet 64:360-364
Todo T, Kondo T, Nakamura S, Kirino T, Kurokawa T, Ikeda K (1998) Neuronal localization of fibroblast growth factor-9 immunoreactivity in human and rat brain. Brain Res 783:179-187
Touriol C, Morillon A, Gensac MC, Prats H, Prats AC (1999) Expression of human fibroblast growth factor 2 mRNA is post-transcriptionally controlled by a unique destabilizing element present in the 3'-untranslated region between alternative polyadenylation sites. J Biol Chem 274:21402-21408
Tsai SJ, Wu MH, Chen HM, Chuang PC, Wing LY (2002) Fibroblast growth factor-9 is an endometrial stromal growth factor. Endocrinology 143:2715-2721
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, et al. (2001) The sequence of the human genome. Science 291:1304-1351
Wilkie GS, Dickson KS, Gray NK (2003) Regulation of mRNA translation by 5'- and 3'-UTR-binding factors. Trends Biochem Sci 28:182-188
Willerton L, Smith RA, Russell D, Mackay S (2004) Effects of FGF9 on embryonic Sertoli cell proliferation and testicular cord formation in the mouse. Int J Dev Biol 48:637-643
Williams AS, Marzluff WF (1995) The sequence of the stem and flanking sequences at the 3' end of histone mRNA are critical determinants for the binding of the stem-loop binding protein. Nucleic Acids Res 23:654-662
Wilson GM, Brewer G (1999) The search for trans-acting factors controlling messenger RNA decay. Prog Nucleic Acid Res Mol Biol 62:257-291
Wilusz CJ, Wormington M, Peltz SW (2001) The cap-to-tail guide to mRNA turnover. Nat Rev Mol Cell Biol 2:237-246
Wing LY, Chuang PC, Wu MH, Chen HM, Tsai SJ (2003) Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen. J Clin Endocrinol Metab 88:5547-5554
Winstall E, Gamache M, Raymond V (1995) Rapid mRNA degradation mediated by the c-fos 3' AU-rich element and that mediated by the granulocyte-macrophage colony-stimulating factor 3' AU-rich element occur through similar polysome-associated mechanisms. Mol Cell Biol 15:3796-3804
Xu N, Chen CY, Shyu AB (1997) Modulation of the fate of cytoplasmic mRNA by AU-rich elements: key sequence features controlling mRNA deadenylation and decay. Mol Cell Biol 17:4611-4621
Zhang T, Kruys V, Huez G, Gueydan C (2002) AU-rich element-mediated translational control: complexity and multiple activities of trans-activating factors. Biochem Soc Trans 30:952-958
Zubiaga AM, Belasco JG, Greenberg ME (1995) The nonamer UUAUUUAUU is the key AU-rich sequence motif that mediates mRNA degradation. Mol Cell Biol 15:2219-2230