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Science 309 (5740): 1514-1518

Copyright © 2005 by the American Association for the Advancement of Science

From Birth to Death: The Complex Lives of Eukaryotic mRNAs

Melissa J. Moore

Abstract: Recent work indicates that the posttranscriptional control of eukaryotic gene expression is much more elaborate and extensive than previously thought, with essentially every step of messenger RNA (mRNA) metabolism being subject to regulation in an mRNA-specific manner. Thus, a comprehensive understanding of eukaryotic gene expression requires an appreciation for how the lives of mRNAs are influenced by a wide array of diverse regulatory mechanisms.

Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, 415 South Street, Waltham, MA 02454. E-mail: mmoore{at}

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Protein segregase meddles in remodeling of mRNA-protein complexes.
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Genes & Dev. 27, 980-984
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The p97-UBXD8 complex destabilizes mRNA by promoting release of ubiquitinated HuR from mRNP.
H.-L. Zhou, C. Geng, G. Luo, and H. Lou (2013)
Genes & Dev. 27, 1046-1058
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EJC core component MLN51 interacts with eIF3 and activates translation.
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UV damage regulates alternative polyadenylation of the RPB2 gene in yeast.
L. Yu and M. R. Volkert (2013)
Nucleic Acids Res. 41, 3104-3114
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J. Biol. Chem. 288, 4908-4921
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M. Saikia, D. Krokowski, B.-J. Guan, P. Ivanov, M. Parisien, G.-f. Hu, P. Anderson, T. Pan, and M. Hatzoglou (2012)
J. Biol. Chem. 287, 42708-42725
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RNA-binding protein AUF1 represses Dicer expression.
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Nucleic Acids Res. 40, 11531-11544
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J. Van Etten, T. L. Schagat, J. Hrit, C. A. Weidmann, J. Brumbaugh, J. J. Coon, and A. C. Goldstrohm (2012)
J. Biol. Chem. 287, 36370-36383
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Bioinformatics 28, 2458-2466
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Nucleic Acids Res. 40, 8637-8645
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C. Liu, X. Zhang, F. Huang, B. Yang, J. Li, B. Liu, H. Luo, P. Zhang, and H. Zhang (2012)
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L. Song, T. Dai, Y. Xie, C. Wang, C. Lin, Z. Wu, Z. Ying, J. Wu, M. Li, and J. Li (2012)
J Mol Cell Biol 4, 108-117
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The post-transcriptional trans-acting regulator, TbZFP3, co-ordinates transmission-stage enriched mRNAs in Trypanosoma brucei.
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D. Dominissini, S. Moshitch-Moshkovitz, N. Amariglio, and G. Rechavi (2011)
Carcinogenesis 32, 1569-1577
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Competitive Regulation of Nucleolin Expression by HuR and miR-494.
K. Tominaga, S. Srikantan, E. K. Lee, S. S. Subaran, J. L. Martindale, K. Abdelmohsen, and M. Gorospe (2011)
Mol. Cell. Biol. 31, 4219-4231
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Enhanced translation by Nucleolin via G-rich elements in coding and non-coding regions of target mRNAs.
K. Abdelmohsen, K. Tominaga, E. K. Lee, S. Srikantan, M.-J. Kang, M. M. Kim, R. Selimyan, J. L. Martindale, X. Yang, F. Carrier, et al. (2011)
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A novel function of Tis11b/BRF1 as a regulator of Dll4 mRNA 3'-end processing.
A. Desroches-Castan, N. Cherradi, J.-J. Feige, and D. Ciais (2011)
Mol. Biol. Cell 22, 3625-3633
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3'UTR elements inhibit Ras-induced C/EBP{beta} post-translational activation and senescence in tumour cells.
S. K. Basu, R. Malik, C. J. Huggins, S. Lee, T. Sebastian, K. Sakchaisri, O. A. Quinones, W. G. Alvord, and P. F. Johnson (2011)
EMBO J. 30, 3714-3728
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Ending the message: poly(A) signals then and now.
N. J. Proudfoot (2011)
Genes & Dev. 25, 1770-1782
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Evolution of Hox Post-Transcriptional Regulation by Alternative Polyadenylation and MicroRNA Modulation Within 12 Drosophila Genomes.
P. Patraquim, M. Warnefors, and C. R. Alonso (2011)
Mol. Biol. Evol. 28, 2453-2460
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EMBO J. 30, 3540-3552
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A. Taylor, B. R. Jackson, M. Noerenberg, D. J. Hughes, J. R. Boyne, M. Verow, M. Harris, and A. Whitehouse (2011)
J. Virol. 85, 7881-7891
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EMBO J. 30, 2622-2633
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Control of human {beta}-globin mRNA stability and its impact on beta-thalassemia phenotype.
I. Peixeiro, A. L. Silva, and L. Romao (2011)
Haematologica 96, 905-913
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The Dbp5 cycle at the nuclear pore complex during mRNA export II: nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1.
K. N. Noble, E. J. Tran, A. R. Alcazar-Roman, C. A. Hodge, C. N. Cole, and S. R. Wente (2011)
Genes & Dev. 25, 1065-1077
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Structure-based prediction of RNA-binding domains and RNA-binding sites and application to structural genomics targets.
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Nucleic Acids Res. 39, 3017-3025
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Mutations in the RNA Granule Component TDRD7 Cause Cataract and Glaucoma.
S. A. Lachke, F. S. Alkuraya, S. C. Kneeland, T. Ohn, A. Aboukhalil, G. R. Howell, I. Saadi, R. Cavallesco, Y. Yue, A. C.-H. Tsai, et al. (2011)
Science 331, 1571-1576
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Mutation of the 5'-Untranslated Region Stem-Loop Structure Inhibits α1(I) Collagen Expression in Vivo.
C. J. Parsons, B. Stefanovic, E. Seki, T. Aoyama, A. M. Latour, W. F. Marzluff, R. A. Rippe, and D. A. Brenner (2011)
J. Biol. Chem. 286, 8609-8619
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An RNA-zipcode-independent mechanism that localizes Dia1 mRNA to the perinuclear ER through interactions between Dia1 nascent peptide and Rho-GTP.
G. Liao, X. Ma, and G. Liu (2011)
J. Cell Sci. 124, 589-599
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The Regulation of Parathyroid Hormone Secretion and Synthesis.
R. Kumar and J. R. Thompson (2011)
J. Am. Soc. Nephrol. 22, 216-224
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S. F. de Almeida, A. Garcia-Sacristan, N. Custodio, and M. Carmo-Fonseca (2010)
Nucleic Acids Res. 38, 8015-8026
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Polyamines Regulate the Stability of JunD mRNA by Modulating the Competitive Binding of Its 3' Untranslated Region to HuR and AUF1.
T. Zou, J. N. Rao, L. Liu, L. Xiao, T.-X. Yu, P. Jiang, M. Gorospe, and J.-Y. Wang (2010)
Mol. Cell. Biol. 30, 5021-5032
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Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules.
D. A. Bosco, N. Lemay, H. K. Ko, H. Zhou, C. Burke, T. J. Kwiatkowski Jr, P. Sapp, D. McKenna-Yasek, R. H. Brown Jr, and L. J. Hayward (2010)
Hum. Mol. Genet. 19, 4160-4175
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Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function.
M. A. Thompson, J. M. Casolari, M. Badieirostami, P. O. Brown, and W. E. Moerner (2010)
PNAS 107, 17864-17871
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Characterization of EMU, the Arabidopsis homolog of the yeast THO complex member HPR1.
C. Furumizu, H. Tsukaya, and Y. Komeda (2010)
RNA 16, 1809-1817
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Developmental RNA processing of 3'UTRs in Hox mRNAs as a context-dependent mechanism modulating visibility to microRNAs.
S. Thomsen, G. Azzam, R. Kaschula, L. S. Williams, and C. R. Alonso (2010)
Development 137, 2951-2960
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Recognition of Polyadenosine RNA by the Zinc Finger Domain of Nuclear Poly(A) RNA-binding Protein 2 (Nab2) Is Required for Correct mRNA 3'-End Formation.
S. M. Kelly, S. W. Leung, L. H. Apponi, A. M. Bramley, E. J. Tran, J. A. Chekanova, S. R. Wente, and A. H. Corbett (2010)
J. Biol. Chem. 285, 26022-26032
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Human G3BP1 interacts with {beta}-F1-ATPase mRNA and inhibits its translation.
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J. Cell Sci. 123, 2685-2696
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Effect of pulmonary rehabilitation on muscle remodelling in cachectic patients with COPD.
I. Vogiatzis, D. C. M. Simoes, G. Stratakos, E. Kourepini, G. Terzis, P. Manta, D. Athanasopoulos, C. Roussos, P. D. Wagner, and S. Zakynthinos (2010)
Eur. Respir. J. 36, 301-310
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SRp40 and SRp55 Promote the Translation of Unspliced Human Immunodeficiency Virus Type 1 RNA.
C. M. Swanson, N. M. Sherer, and M. H. Malim (2010)
J. Virol. 84, 6748-6759
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A Review of Methods to Monitor the Modulation of mRNA Stability: A Novel Approach to Drug Discovery and Therapeutic Intervention.
D. Cheneval, T. Kastelic, P. Fuerst, and C. N. Parker (2010)
J Biomol Screen 15, 609-622
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Structural and functional analysis of the interaction between the nucleoporin Nup98 and the mRNA export factor Rae1.
Y. Ren, H.-S. Seo, G. Blobel, and A. Hoelz (2010)
PNAS 107, 10406-10411
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The life of an mRNA in space and time.
Y. Ben-Ari, Y. Brody, N. Kinor, A. Mor, T. Tsukamoto, D. L. Spector, R. H. Singer, and Y. Shav-Tal (2010)
J. Cell Sci. 123, 1761-1774
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Stress granule formation mediates the inhibition of colonic Hsp70 translation by interferon-{gamma} and tumor necrosis factor-{alpha}.
S. Hu, E. C. Claud, M. W. Musch, and E. B. Chang (2010)
Am J Physiol Gastrointest Liver Physiol 298, G481-G492
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Tandem Phosphorylation of Serines 221 and 318 by Protein Kinase C{delta} Coordinates mRNA Binding and Nucleocytoplasmic Shuttling of HuR.
A. Doller, K. Schlepckow, H. Schwalbe, J. Pfeilschifter, and W. Eberhardt (2010)
Mol. Cell. Biol. 30, 1397-1410
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A global comparison between nuclear and cytosolic transcriptomes reveals differential compartmentalization of alternative transcript isoforms.
L. Chen (2010)
Nucleic Acids Res. 38, 1086-1097
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Nonsense-Mediated RNA Decay Regulation by Cellular Stress: Implications for Tumorigenesis.
L. B. Gardner (2010)
Mol. Cancer Res. 8, 295-308
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An unexpected ending: Noncanonical 3' end processing mechanisms.
J. E. Wilusz and D. L. Spector (2010)
RNA 16, 259-266
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NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif.
Y. Kuwano, R. Pullmann Jr., B. S. Marasa, K. Abdelmohsen, E. K. Lee, X. Yang, J. L. Martindale, M. Zhan, and M. Gorospe (2010)
Nucleic Acids Res. 38, 225-238
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K. G. Chernov, A. Barbet, L. Hamon, L. P. Ovchinnikov, P. A. Curmi, and D. Pastre (2009)
J. Biol. Chem. 284, 36569-36580
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Mammalian pre-mRNA 3' End Processing Factor CF Im68 Functions in mRNA Export.
M.-D. Ruepp, C. Aringhieri, S. Vivarelli, S. Cardinale, S. Paro, D. Schumperli, and S. M.L. Barabino (2009)
Mol. Biol. Cell 20, 5211-5223
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Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines.
X. Zhang, T. Zou, J. N. Rao, L. Liu, L. Xiao, P.-Y. Wang, Y.-H. Cui, M. Gorospe, and J.-Y. Wang (2009)
Nucleic Acids Res. 37, 7623-7637
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Tandem KH domains of Khd4 recognize AUACCC and are essential for regulation of morphology as well as pathogenicity in Ustilago maydis.
E. Vollmeister, C. Haag, K. Zarnack, S. Baumann, J. Konig, G. Mannhaupt, and M. Feldbrugge (2009)
RNA 15, 2206-2218
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IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes.
J. Christiansen, A. M Kolte, T. v O Hansen, and F. C Nielsen (2009)
J. Mol. Endocrinol. 43, 187-195
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Role for Kruppel-Like Factor 4 in Determining the Outcome of p53 Response to DNA Damage.
Q. Zhou, Y. Hong, Q. Zhan, Y. Shen, and Z. Liu (2009)
Cancer Res. 69, 8284-8292
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Increased MKK4 Abundance with Replicative Senescence Is Linked to the Joint Reduction of Multiple MicroRNAs.
B. S. Marasa, S. Srikantan, K. Masuda, K. Abdelmohsen, Y. Kuwano, X. Yang, J. L. Martindale, C. W. Rinker-Schaeffer, and M. Gorospe (2009)
Science Signaling 2, ra69
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