Translational Control Of Gene Expression Research Articles

Meal Feeding Alters Translational Control of Gene Expression in Rat Liver

Meal feeding after a period of food deprivation results in a subsequent increase in the protein and RNA content of the liver. To gain insight into the mechanisms involved in the response to food intake, changes in the association of selected mRNAs with polysomes were examined. On the day of the study, rat livers were collected at 0, 15, 60, and 180 min after the start of feeding and analyzed for biomarkers of the translational control of protein synthesis. Protein synthesis was increased within 60 min and was sustained for 180 min. Assembly of the active eukaryotic initiation factor (eIF) 4F complex was elevated within 15 min, as indicated by the relative association of eIF4E . eIF4G, but returned to the basal value within 180 min. Phosphorylation of the ribosomal protein (rp) S6 kinase S6K1 and its substrate rpS6 was increased within 15 min and was sustained for at least 180 min. Both eIF4F assembly and activation of S6K1 have been linked to upregulated translation of a subset of mRNAs. To identify translationally regulated mRNAs, polysomal (i.e., actively translated) and nonpolysomal (nontranslated) fractions were isolated and subjected to microarray analysis. The mRNAs encoding 78 proteins, including 42 proteins involved in protein synthesis, exhibited increased abundance in polysomes in response to feeding. Overall, the results demonstrate that protein synthesis as well as ribosomal protein mRNA translation undergo rapid and sustained stimulation in the liver after meal feeding and thus contribute to the previously observed increases in protein and RNA content.

Mouse p56 Blocks a Distinct Function of Eukaryotic Initiation Factor 3 in Translation Initiation

Members of the p56 family of mammalian proteins are strongly induced in virus-infected cells and in cells treated with interferons or double-stranded RNA. Previously, we have reported that human p56 inhibits initiation of translation by binding to the "e" subunit of eukaryotic initiation factor 3 (eIF3) and subsequently interfering with the eIF3/eIF2.GTP.Met-tRNAi (ternary complex) interaction. Here we report that mouse p56 also interferes with eIF3 functions and inhibits translation. However, the murine protein binds to the "c" subunit, not the "e" subunit, of eIF3. Consequently, it has only a marginal effect on eIF3.ternary complex interaction. Instead, the major inhibitory effect of mouse p56 is manifested at a different step of translation initiation, namely the binding of eIF4F to the 40 S ribosomal subunit.eIF3.ternary complex. Thus, mouse and human p56 proteins block different functions of eIF3 by binding to its different subunits.

All-trans-Retinoic acid (ATRA) and Arsenic Trioxide-Induced Expression and Regulation of Programmed Cell Death 4 (PDCD4) in Acute Promyelocytic Leukemia.

All-trans-retinoic acid (ATRA) induces growth inhibition, differentiation and apoptosis in acute promyelocytic leukemia (APL) characterized by t(15;17), which leads to expression of PML-RARa and differentiation arrest. ATRA treatment alone results in complete remission (CR) about 90% of APL patients. However these remissions are transient and APL patients commonly become resistant to ATRA therapy. Recently, arsenic trioxide, As(2)O(3), was proven to be highly effective in inducing CRs not only in relapsed after ATRA and primary APL patients. Despite the well documented clinical efficacy ATRA and As(2)O(3) in APL, precise downstream molecular mechanisms of action of these agents and the molecular mechanisms responsible for the resistance largely remain unknown. Recently, employing comprehensive proteomics methods we studied molecular mechanisms of ATRA-induced growth inhibition in APL cells. We reported that ATRA induces translational suppression through multiple posttranscriptional mechanisms involved in translation initiation and elongation phases (Harris &Ozpolat et al, Blood, 104 (5) 2004). We also demonstrated that ATRA inhibits expression translation initiation factors including IF2, eIF4AI, eIF4G, eIF5, eIF6 but upregulates expression of translation inhibitor DAP5/p97/NAT1 in APL cells. Translational control of gene expression has been identified as an important regulatory mechanism for gene products involved in regulation of cell proliferation, differentiation and apoptosis. Programmed cell death 4(PDCD4) inhibits cap-dependent translation and exerts transformation-suppressing activity by inhibiting the helicase activity of eIF4A. . Here we investigated whether PDCD4 plays a role in ATRA-induced growth inhibition and terminal differentiation by mediating translational suppression. We found for the first time that ATRA (1 mM) and As(2)O(3) ( 0.4 mM and 2 mM) induced PDCD4 expression at mRNA and protein level detected by RT-PCR and western blotting analyses, respectively, after 24 h of treatment in NB4 cells. As(2)O(3) induced maximum PDCD4 protein expression at 72 h of treatment in NB4 cells ATRA induced PDCD4 mRNA expression in ATRA responsive human acute myeloid leukemia cells (HL-60) but not in ATRA-resistant HL60 cells (HL-60R), which express a point mutation in ATRA binding domain of RARa, suggesting PDCD4 expression is mediated through retinoid receptor alpha in HL-60 leukemia cells. Overall data suggest that translational control may play a role in ATRA-induced differentiation and As(2)O(3)-induced effects. We are currently determining whether other retinoid receptors are involved in ATRA-induced expression of PDCD4 and testing the hypothesis that whether PDCD4-mediated translational suppression is critical to ATRA-induced APL cell differentiation. Activation of these pathways that lead to translational suppression reveals a novel mechanism of ATRA action and provide novel insights into ATRA-induced differentiation program in APL cells.Better understanding of posttranscriptional control of gene expression may offer targets for the differentiation therapy and chemo preventive strategies.

Temporal complexity within a translational control element in thenanosmRNA

Translational control of gene expression plays a fundamental role in the early development of many organisms. In Drosophila, selective translation of nanos mRNA localized to the germ plasm at the posterior of the embryo, together with translational repression of nanos in the bulk cytoplasm, is essential for development of the anteroposterior body pattern. We show that both components to spatial control of nanos translation initiate during oogenesis and that translational repression is initially independent of Smaug, an embryonic repressor of nanos. Repression during oogenesis and embryogenesis are mediated by distinct stem loops within the nanos 3' untranslated region; the Smaug-binding stem-loop acts strictly in the embryo, whereas a second stem-loop functions in the oocyte. Thus, independent regulatory modules with temporally distinct activities contribute to spatial regulation of nanos translation. We propose that nanos evolved to exploit two different stage-specific translational regulatory mechanisms.

SiRNA for gene silencing: a route to drug target discovery.

The identification of RNA interference in mammalian cells, mediated via both virally-derived short interference RNA (siRNA) and endogenously produced microRNA, has revolutionised our understanding of the translational control of gene expression. Indeed, since its initial discovery, siRNA has been rapidly deployed for the elucidation of gene function and the identification of potential drug targets, a process often known as target discovery. In this review, we briefly discuss the mechanism of RNA interference and then critically examine the use of siRNA in target discovery, with a particular emphasis upon issues such as efficacy, selectivity, delivery and application in high-throughput studies.

Identification of a Novel Internal Ribosome Entry Site in Giardiavirus That Extends to Both Sides of the Initiation Codon

In Giardia lamblia, enhanced translation of luciferase mRNA, flanked between the 5'-untranslated region (UTR) and 3 '-end of giardiavirus transcript, requires the presence of the initial 264-nucleotide (nt) viral capsid-coding region. By introducing the transcripts of dicistronic viral constructs into Giardia, we demonstrated that the 264-nt downstream region alone is insufficient to function as an internal ribosome entry site (IRES) without including a portion of the 5 '-UTR as well. Deletion analysis showed that efficient internal initiation requires the last 253 nts (nts 114-367) of the 5 '-UTR in combination with the downstream 264 nts. Specific mutations that disrupted the predicted secondary structural elements in either the 5 '-UTR or the 264-nt capsid-coding region completely abolished the IRES-mediated translation of downstream cistron, suggesting that the IRES activity requires the presence of these structures in both regions. Mutations that abolished translation of the first cistron did not, however, affect the IRES-mediated translation of the second cistron, indicating that this IRES-mediated translation is independent of the translation of the upstream cistron. This is, to our knowledge, the first reported identification of a viral IRES with an estimated size of 517 nts that extends to both sides of the initiation site.

Two zebrafish eIF4E family members are differentially expressed and functionally divergent.

Eukaryotic translation initiation factor 4E (eIF4E) is an essential component of the translational machinery that binds m(7)GTP and mediates the recruitment of capped mRNAs by the small ribosomal subunit. Recently, a number of proteins with homology to eIF4E have been reported in plants, invertebrates, and mammals. Together with the prototypical translation factor, these constitute a new family of structurally related proteins. To distinguish the prototypical translation factor eIF4E from other family members, it has been termed eIF4E-1 (Keiper, B. D., Lamphear, B. J., Deshpande, A. M., Jankowska-Anyszka, M., Aamodt, E. J., Blumenthal, T., and Rhoads, R. E. (2000) J. Biol. Chem. 275, 10590-10596). We describe the characterization of two eIF4E family members in the zebrafish Danio rerio. Based on their relative identities with human eIF4E-1, these zebrafish proteins are termed eIF4E-1A (82%) and eIF4E-1B (66%). eIF4E-1B, originally termed eIF4E(L), has been reported previously as the zebrafish eIF4E-1 counterpart (Fahrenkrug, S. C., Dahlquist, M. O., Clark, K., and Hackett, P. B. (1999) Differentiation 65, 191-201; Fahrenkrug, S. C., Joshi, B., Hackett, P. B., and Jagus, R. (2000) Differentiation 66, 15-22). Sequence comparisons suggest that the two genes probably evolved from a duplication event that occurred during vertebrate evolution. eIF4E-1A is expressed ubiquitously in zebrafish, whereas expression of eIF4E-1B is restricted to early embryonic development and to gonads and muscle of the tissues investigated. The ability of these two zebrafish proteins to bind m(7)GTP, eIF4G, and 4E-BP, as well as to complement yeast conditionally deficient in functional eIF4E, show that eIF4E-1A is a functional equivalent of human eIF4E-1. Surprisingly, although eIF4E-1B possesses all known residues thought to be required for interaction with the cap structure, eIF4G, and 4E-BPs, it fails to interact with any of these components, suggesting that this protein serves a role other than that assigned to eIF4E.

Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue.

Eukaryotic initiation factor (eIF) 2B catalyzes the nucleotide activation of eIF2 to its active GTP-bound state. The exchange activity has been mapped to the C terminus of the eIF2Bepsilon subunit. We have determined the crystal structure of residues 544-704 from yeast eIF2Bepsilon at 2.3-A resolution, and this fragment is an all-helical protein built around the conserved aromatic acidic (AA) boxes also found in eIF4G and eIF5. The eight helices are organized in a manner similar to HEAT repeats. The molecule is highly asymmetric with respect to surface charge and conservation. One area in the N terminus is proposed to be directly involved in catalysis. In agreement with this hypothesis, mutation of glutamate 569 is shown to be lethal. An acidic belt and a second area in the C terminus containing residues from the AA boxes are important for binding to eIF2. Two mutations causing the fatal human genetic disease leukoencephalopathy with vanishing white matter are buried and appear to disrupt the structural integrity of the catalytic domain rather than interfering directly with catalysis or binding of eIF2.

New paradigms for nutrient control of genome translation.

Organisms respond adaptively to changing environmental conditions by altering genome expression. Translational control of gene expression by nutrients and metabolites is one of the most robust biologic mechanisms that enable rapid alterations in the cellular proteome in response to changes in the local environment. Recently, investigators have identified new mechanisms for nutrient control of translation in mammals; evidence supports the conservation of translational control mechanisms in eukaryotes that heretofore had only been demonstrated in prokaryotes.

The function of SECIS RNA in translational control of gene expression in Escherichia coli.

The incorporation of selenocysteine into proteins is directed by specific UGA codons and mRNA secondary structures, designated SECIS elements. In bacteria, these elements are positioned within the reading frame of selenoprotein mRNAs immediately downstream of the triplet coding for selenocysteine, and they tether a complex of the selenocysteine-specific elongation factor SelB, GTP and selenocysteyl-tRNA(Sec) to the site of UGA decoding. A SECIS-like structure was identified in the 5' non-translated region of the selAB transcript, encoding selenocysteine synthase and SelB. It specifically binds to SelB and the formation of a SelB.GTP.selenocysteyl-tRNA(Sec) complex on the SECIS-like element represses expression of the downstream gene. This effect is abolished by mutations preventing formation of the complex. The regulatory pattern observed correlated with the levels of sel gene products. As quaternary complex formation on the SECIS-like element did not influence the transcription rate and only slightly reduced the level of selAB mRNA, it was concluded that the structure is involved in regulating translation initiation efficiency, thereby coupling selenocysteine biosynthesis to the availability of the trace element selenium.

Beta 2-adrenergic receptor stimulated, G protein-coupled receptor kinase 2 mediated, phosphorylation of ribosomal protein P2.

G protein-coupled receptor kinases are well characterized for their ability to phosphorylate and desensitize G protein-coupled receptors (GPCRs). In addition to phosphorylating the beta2-adrenergic receptor (beta2AR) and other receptors, G protein-coupled receptor kinase 2 (GRK2) can also phosphorylate tubulin, a nonreceptor substrate. To identify novel nonreceptor substrates of GRK2, we used two-dimensional gel electrophoresis to find cellular proteins that were phosphorylated upon agonist-stimulation of the beta2AR in a GRK2-dependent manner. The ribosomal protein P2 was identified as an endogenous HEK-293 cell protein whose phosphorylation was increased following agonist stimulation of the beta2AR under conditions where tyrosine kinases, PKC and PKA, were inhibited. P2 along with its other family members, P0 and P1, constitutes a part of the elongation factor-binding site connected to the GTPase center in the 60S ribosomal subunit. Phosphorylation of P2 is known to regulate protein synthesis in vitro. Further, P2 and P1 are shown to be good in vitro substrates for GRK2 with K(M) values approximating 1 microM. The phosphorylation sites in GRK2-phosphorylated P2 are identified (S102 and S105) and are identical to the sites known to regulate P2 activity. When the 60S subunit deprived of endogenous P1 and P2 is reconstituted with GRK2-phosphorylated P2 and unphosphorylated P1, translational activity is greatly enhanced. These findings suggest a previously unrecognized relationship between GPCR activation and the translational control of gene expression mediated by GRK2 activation and P2 phosphorylation and represent a potential novel signaling pathway responsible for P2 phosphorylation in mammals.

Translational control of gene expression: Role of IRESs and consequences for cell transformation and angiogenesis

Translational control of gene expression has, over the last 10 years, become appreciated as an important process in its regulation in eukaryotes. Among a series of control mechanisms exerted at the translational level, the use of alternative codons provides a very subtle means of increasing gene diversity by expressing several proteins from a single mRNA. The internal ribosome entry sites (IRESs) act as specific translational enhancers that allow translation initiation to occur independently of the classic cap-dependent mechanism, in response to specific stimuli and under the control of different trans-acting factors. It is striking to observe that the two processes mostly concern genes coding for control proteins such as growth factors, protooncogenes, angiogenesis factors, and apoptosis regulators. Here, we focus on the translational regulation of four mRNAs, with both IRESs and alternative initiation codons, which are the messengers of retroviral murine leukemia virus, fibroblast growth factor 2, vascular endothelial growth factor, and protooncogene c-myc. Four of them are involved in cell transformation and/or angiogenesis, with important consequences for such translation regulations in these pathophysiological processes.

Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency.

Although the physiological role of tissue-specific translational control of gene expression in mammals has long been suspected on the basis of biochemical studies, direct evidence has been lacking. Here, we report on the targeted disruption of the gene encoding the heme-regulated eIF2alpha kinase (HRI) in mice. We establish that HRI, which is expressed predominantly in erythroid cells, regulates the synthesis of both alpha- and beta-globins in red blood cell (RBC) precursors by inhibiting the general translation initiation factor eIF2. This inhibition occurs when the intracellular concentration of heme declines, thereby preventing the synthesis of globin peptides in excess of heme. In iron-deficient HRI(-/-) mice, globins devoid of heme aggregated within the RBC and its precursors, resulting in a hyperchromic, normocytic anemia with decreased RBC counts, compensatory erythroid hyperplasia and accelerated apoptosis in bone marrow and spleen. Thus, HRI is a physiological regulator of gene expression and cell survival in the erythroid lineage.

The Carboxyl-terminal Domain of the Granulocyte Colony-stimulating Factor Receptor Uncouples Ribosomal Biogenesis from Cell Cycle Progression in Differentiating 32D Myeloid Cells

Translational regulation plays an important role in development. In terminally differentiating cells a decrease in translation rate is common, although the regulatory mechanisms are unknown. We utilized 32Dcl3 myeloblast cells to investigate translational regulation during granulocyte colony-stimulating factor (G-CSF)-induced differentiation. G-CSF causes a significant decrease in translation rate compared with interleukin-3, which is a mitogen for these cells. Although these two cytokines exhibit modest differences in their effect on translation factor phosphorylation, they exhibit dramatic differences in their effect on ribosomal abundance and ribosomal DNA transcription. However, because both cytokines stimulate cell cycling, G-CSF induces a dissociation of ribosomal biogenesis from cell cycle progression. This uncoupling of ribosomal biogenesis from cell cycle progression appears to be closely related to the transmission of a differentiation signal, because it is not observed in cells expressing a carboxyl-terminally truncated G-CSF receptor, which supports proliferation but not differentiation of these cells. Because a similar event occurs early in differentiation of murine erythroleukemic cells, this suggests that ribosomal content is a common target of differentiating agents.

Unleashing yeast genetics on a factor-independent mechanism of internal translation initiation.

Translational control of gene expression is generally exerted in the initiation phase of protein synthesis. The reactions of the initiation pathway bring the ribosome to the mRNA and place the initiation codon in the peptidyl (P) site of the ribosome, base-paired with the anticodon of methionyl initiator tRNA (Met-tRNA). The aminoacyl (A) site in the ribosome is left open to accept the elongator tRNA that decodes the second codon in the ORF. Formation of this 80S initiation complex in eukaryotic cells depends on 11 or more soluble initiation factors (eIFs), identified primarily through biochemical studies of translation in rabbit reticulocyte extracts. Most of these eIFs are essential for normal cell growth in budding yeast, confirming their importance in vivo (1). Nevertheless, a number of mRNAs contain specialized regulatory elements that allow them to dispense with one or more eIFs during translation initiation. These elements, called internal ribosome entry sites (IRESs), recruit the ribosome directly to the initiation region of the mRNA. Their independence of certain eIFs allows viral mRNAs containing IRESs to be translated in infected cells where one or more eIFs have been impaired, either by the virus to provide a selective advantage for its mRNAs or by the host to impede virus gene expression. The most striking instance of this strategy is provided by cricket paralysis virus (CrPV) mRNA, which seems to be translated without any eIFs or even Met-tRNA (2). The work reported by Sarnow and colleagues (3) in this issue of PNAS shows that the unique CrPV initiation mechanism can operate in budding yeast cells, so long as the canonical initiation pathway involving initiation factor 2 (eIF2) has been impaired. These findings open up the possibility of using powerful yeast genetics to dissect the details of this remarkable mechanism and to define the factors that modulate its efficiency in living cells.

Mutational analysis of the different bulge regions of hepatitis C virus domain II and their influence on internal ribosome entry site translational ability.

The hepatitis C virus (HCV) 5'-untranslated region and, in particular, domains II to IV are involved in the internal ribosome entry site (IRES) structure. Recent structural evidence has shown that the function of domain II may be to hold the coding RNA in position until the translational machinery is correctly assembled on the decoding site. However, a comprehensive mutational and functional study concerning the importance of the different RNA regions that compose domain II is not yet available. Therefore, we have taken advantage of the recently proposed secondary structure of domain II to design a series of specific mutants. The bulge regions present in the latest secondary structure prediction of domain II were selectively deleted, and the effects of these mutations on IRES translation efficiency were analyzed. Our results show that the introduction of these mutations can variably affect the degree of HCV translation, causing a moderate to total loss of translation ability that correlates with the severity of changes induced in the RNA secondary structure and degree of p25 ribosomal protein UV cross-linking, but not with the ability of the 40S ribosomal subunit to bind the IRES. These findings support the proposed structural role of domain II in HCV translation.

Translational control of gene expression

Translational control of gene expression

The cytoplasmic fate of mRNA

Translational Control of Gene Expression edited by N. Sonenberg, J. W. B. Hershey and M. B. Matthews Cold Spring Harbor Laboratory Press (2000) 1020 pages. ISBN 0–87969-568-4 US$115 At the beginning of the 90s most molecular biologists were focusing on transcription and RNA splicing. mRNA translation and its temporal and spatial regulation seemed research topics for insiders at that time. However, all aspects of mRNA fate in the cytoplasm will certainly attract much more attention during the next decade. The field is now flourishing with connections to all disciplines of biology. This book will help you to realize the tremendous variation of translational regulatory mechanisms existing in nature. The evidence for their importance has become so overwhelming that nobody seriously interested in gene expression can ignore it any longer. It is the great merit of the editors of this book that they have brought together an impressive series of first-class reviews written by the most prominent scientists in the field. The new monograph takes a fresh look at the field and is greatly expanded compared with the earlier 1996 version. The book is judiciously divided into two parts. The first part comprises eight broad chapters, giving an overview of the main principles of protein synthesis and its regulation. They serve as a thorough basis for the second part, which comprises twenty-eight chapters, each about 20 pages in length, that present in depth additional exciting areas in which there is strong research activity. Your appetite for this book will be stimulated right at the beginning by the wonderful introductory chapter, which is written jointly by the editors and defines the field in its entire complexity. Given that translation is of course a unifying principle of all living organisms, why are there such a large number of different control mechanisms modulating the use of mRNA templates and making actual protein level not predictable from RNA quantity alone? Are these just remnants of an RNA world or, as the authors seem to believe, effective adaptations for fine-tuning gene expression that have been opportunistically added during evolution? Five broad chapters are devoted to our knowledge of initiation, elongation and termination of translation both in eukaryotes and in prokaryotes. It is amazing how much detail has been added, in just the past five years, to our picture of the biochemistry, structure and function of ribosomes, initiation sites, and translation factors. However, translational control of gene expression is not just a matter of the translation machinery alone. It seems rather that the tremendously versatile mRNA sequences and structures impose the way they are seen by the translation apparatus and its factors. Particularly in eukaryotes, the untranslated parts of mRNAs play a decisive role by providing additional interaction sites for cytoplasmic proteins that modulate mRNA stability, mRNA localization or accessibility of mRNAs to translation. In turn, many of the proteins interacting with mRNA are themselves regulated by metabolites or post-translational modifications. This is beautifully documented in an exciting chapter on the role of translational control in developmental decisions. For example, in Drosophila, a specific cascade of factors acting on RNA localization and translation controls the anterior-posterior body axis. In C. elegans, the fate of germ-line cells is determined by translational repression. And you will find many more such examples. Another important section of the book is devoted to changes in translation that occur during virus infection. Again one is amazed by the variety of ways by which viruses divert the host translation apparatus for their own sake. The shorter chapters give insight into additional exciting areas in the field. For example, research into how heat shock or signal transduction pathways feed into translation, what we know about mRNA degradation of normal and nonsense-containing transcripts, and the evidence that local synaptic protein synthesis represents a molecular hallmark of learning and memory. This book is the most complete and up-to-date review of translational control mechanisms. It is a must for students entering the field, and it will constitute for many years a major reference guide for any investigator who is seriously interested in the full picture of gene expression.

Translational Control of Gene Expression, edited by Nahum Sonenberg, John W.B. Hershey, and Michael B. Mathews. 2000. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press. Cloth, 1,020 pp. $113.

For two decades, up to the mid-1980s, study of the translation phase of gene expression was conducted by a relatively small group of protein biochemistry, cell physiology, and developmental biology labs. These workers labored against a widely held view that anything and everything exciting in the control of gene expression must occur at the level of transcription. Since that time, however, the use of molecular genetics has revealed an amazing array of mechanisms for regulating both overall protein synthesis and selective control of translation of individual mRNAs in response to physiological conditions. This led to a remarkable influx of workers into the field, severely challenging the catering facilities at the Cold Spring Harbor Laboratory during the biannual meetings on Translational Control, which were inaugurated in 1987. The first Cold Spring Harbor “Translational Control” monograph was published in 1996, and its excellent articles have provided a valuable resource to established workers and newcomers alike. However, it is a reflection of the rapid development of knowledge in this field that this volume now looks decidedly middle-aged. It was therefore decided to produce a new volume of articles for the year 2000. Although a few of the 36 chapters in the new monograph are necessary updates of subjects covered previously, by far the majority of the articles are by different authors and cover new directions, many of which were barely a gleam in the eye in 1996.

A Progress Report on Translational Control in Eukaryotes

An extraordinary amount of regulation goes into making sure that protein expression is controlled correctly. Several layers of regulation function to achieve the proper levels and proper timing of protein expression. Much is known about the protein machinery involved in translation, but we are lagging behind in understanding the mechanisms of control in eukaryotes. Kozak reviews the new second edition of Translational Control of Gene Expression, which attempts to catalog the mechanisms used by prokaryotes and eukaryotes, and the viruses that infect them and subvert their translational machinery.