an mrna has the stop codon 5 uaa 3. what trna anticodon will bind to it?

Proteins are synthesized from mRNA templates by a process that has been highly conserved throughout evolution (reviewed in Chapter 3). All mRNAs are read in the 5´ to three´ direction, and polypeptide chains are synthesized from the amino to the carboxy terminus. Each amino acrid is specified by iii bases (a codon) in the mRNA, according to a nearly universal genetic code. The basic mechanics of protein synthesis are also the same in all cells: Translation is carried out on ribosomes, with tRNAs serving as adaptors between the mRNA template and the amino acids beingness incorporated into poly peptide. Protein synthesis thus involves interactions between three types of RNA molecules (mRNA templates, tRNAs, and rRNAs), equally well as various proteins that are required for translation.

Transfer RNAs

During translation, each of the 20 amino acids must be aligned with their corresponding codons on the mRNA template. All cells contain a variety of tRNAs that serve as adaptors for this process. As might be expected, given their mutual function in protein synthesis, different tRNAs share similar overall structures. However, they too possess unique identifying sequences that allow the right amino acid to be fastened and aligned with the appropriate codon in mRNA.

Transfer RNAs are approximately 70 to 80 nucleotides long and have characteristic cloverleaf structures that upshot from complementary base pairing between different regions of the molecule (Figure 7.1). X-ray crystallography studies take farther shown that all tRNAs fold into similar compact L shapes, which are likely required for the tRNAs to fit onto ribosomes during the translation process. The adaptor function of the tRNAs involves two separated regions of the molecule. All tRNAs have the sequence CCA at their 3´ terminus, and amino acids are covalently attached to the ribose of the terminal adenosine. The mRNA template is then recognized by the anticodon loop, located at the other end of the folded tRNA, which binds to the appropriate codon past complementary base pairing.

Figure 7.1

Construction of tRNAs. The structure of yeast phenylalanyl tRNA is illustrated in open "cloverleaf" form (A) to evidence complementary base pairing. Modified bases are indicated every bit mG, methylguanosine; mC, methylcytosine; DHU, dihydrouridine; (more...)

The incorporation of the correctly encoded amino acids into proteins depends on the attachment of each amino acid to an appropriate tRNA, every bit well as on the specificity of codon-anticodon base of operations pairing. The zipper of amino acids to specific tRNAs is mediated by a group of enzymes called aminoacyl tRNA synthetases, which were discovered past Paul Zamecnik and Mahlon Hoagland in 1957. Each of these enzymes recognizes a single amino acrid, equally well as the correct tRNA (or tRNAs) to which that amino acid should be attached. The reaction gain in ii steps (Figure vii.2). Starting time, the amino acid is activated past reaction with ATP to course an aminoacyl AMP synthetase intermediate. The activated amino acid is so joined to the iii´ terminus of the tRNA. The aminoacyl tRNA synthetases must exist highly selective enzymes that recognize both individual amino acids and specific base sequences that identify the correct acceptor tRNAs. In some cases, the high fidelity of amino acid recognition results in part from a proofreading function by which incorrect aminoacyl AMPs are hydrolyzed rather than being joined to tRNA during the 2d step of the reaction. Recognition of the right tRNA by the aminoacyl tRNA synthetase is also highly selective; the synthetase recognizes specific nucleotide sequences (in near cases including the anticodon) that uniquely identify each species of tRNA.

Figure 7.ii

Zipper of amino acids to tRNAs. In the first reaction stride, the amino acid is joined to AMP, forming an aminoacyl AMP intermediate. In the 2nd pace, the amino acid is transferred to the 3´ CCA terminus of the acceptor tRNA and AMP is released. (more than...)

After being attached to tRNA, an amino acid is aligned on the mRNA template past complementary base pairing between the mRNA codon and the anticodon of the tRNA. Codon-anticodon base pairing is somewhat less stringent than the standard A-U and G-C base pairing discussed in preceding chapters. The significance of this unusual base of operations pairing in codon-anticodon recognition relates to the back-up of the genetic code. Of the 64 possible codons, three are stop codons that signal the termination of translation; the other 61 encode amino acids (see Table 3.1). Thus, most of the amino acids are specified by more i codon. In part, this redundancy results from the zipper of many amino acids to more than than one species of tRNA. E. coli, for instance, contain about 40 different tRNAs that serve as acceptors for the xx different amino acids. In addition, some tRNAs are able to recognize more than one codon in mRNA, as a consequence of nonstandard base pairing (called wobble) betwixt the tRNA anticodon and the third position of some complementary codons (Effigy 7.3). Relaxed base pairing at this position results partly from the formation of One thousand-U base pairs and partly from the modification of guanosine to inosine in the anticodons of several tRNAs during processing (meet Figure vi.38). Inosine can base-pair with either C, U, or A in the third position, and so its inclusion in the anticodon allows a single tRNA to recognize three different codons in mRNA templates.

Figure 7.3

Nonstandard codon-anticodon base pairing. Base pairing at the third codon position is relaxed, allowing Chiliad to pair with U, and inosine (I) in the anticodon to pair with U, C, or A. Two examples of aberrant base pairing, assuasive phenylalanyl (Phe) tRNA (more...)

The Ribosome

Ribosomes are the sites of protein synthesis in both prokaryotic and eukaryotic cells. Offset characterized as particles detected past ultracentrifugation of prison cell lysates, ribosomes are commonly designated according to their rates of sedimentation: 70S for bacterial ribosomes and 80S for the somewhat larger ribosomes of eukaryotic cells. Both prokaryotic and eukaryotic ribosomes are composed of two distinct subunits, each containing characteristic proteins and rRNAs. The fact that cells typically contain many ribosomes reflects the central importance of protein synthesis in cell metabolism. Due east. coli, for example, contain about 20,000 ribosomes, which account for approximately 25% of the dry weight of the cell, and apace growing mammalian cells contain nearly ten 1000000 ribosomes.

The general structures of prokaryotic and eukaryotic ribosomes are similar, although they differ in some details (Effigy vii.4). The small subunit (designated 30S) of E. coli ribosomes consists of the 16S rRNA and 21 proteins; the large subunit (50S) is composed of the 23S and 5S rRNAs and 34 proteins. Each ribosome contains i re-create of the rRNAs and 1 copy of each of the ribosomal proteins, with one exception: 1 poly peptide of the 50S subunit is present in four copies. The subunits of eukaryotic ribosomes are larger and contain more proteins than their prokaryotic counterparts have. The small subunit (40S) of eukaryotic ribosomes is composed of the 18S rRNA and approximately 30 proteins; the large subunit (60S) contains the 28S, 5.8S, and 5S rRNAs and nearly 45 proteins.

Figure 7.4

Ribosome structure. (A) Electron micrograph of E. coli 50S ribosomal subunits. (B–C) High resolution Ten-ray crystal structures of 30S (B) and 50S (C) ribosomal subunits. (D) Model of ribosome structure. (Eastward) Components of prokaryotic and eukaryotic (more...)

A noteworthy characteristic of ribosomes is that they can exist formed in vitro by self-assembly of their RNA and protein constituents. Every bit kickoff described in 1968 by Masayasu Nomura, purified ribosomal proteins and rRNAs can be mixed together and, under appropriate conditions, will reform a functional ribosome. Although ribosome assembly in vivo (particularly in eukaryotic cells) is considerably more complicated, the ability of ribosomes to self-assemble in vitro has provided an of import experimental tool, allowing analysis of the roles of individual proteins and rRNAs.

Like tRNAs, rRNAs form characteristic secondary structures by complementary base pairing (Figure 7.5). In association with ribosomal proteins the rRNAs fold further, into distinct three-dimensional structures. Initially, rRNAs were thought to play a structural part, providing a scaffold upon which ribosomal proteins assemble. However, with the discovery of the catalytic activity of other RNA molecules (due east.one thousand., RNase P and the self-splicing introns discussed in Chapter 6), the possible catalytic role of rRNA became widely considered. Consistent with this hypothesis, rRNAs were found to be absolutely required for the in vitro assembly of functional ribosomes. On the other hand, the omission of many ribosomal proteins resulted in a decrease, but not a complete loss, of ribosome action.

Figure seven.5

The structure of 16S rRNA. Complementary base of operations pairing results in the formation of a distinct secondary structure. (From South. Stern, T. Powers, L.-I. Changchien and H. F. Noller, 1989. Science 244: 783.)

Directly evidence for the catalytic activity of rRNA start came from experiments of Harry Noller and his colleagues in 1992. These investigators demonstrated that the large ribosomal subunit is able to catalyze the formation of peptide bonds (the peptidyl transferase reaction) even after approximately 95% of the ribosomal proteins have been removed by standard protein extraction procedures. In contrast, treatment with RNase completely abolishes peptide bail germination, providing strong support for the hypothesis that the germination of a peptide bond is an RNA-catalyzed reaction. Farther studies have confirmed and extended these results by demonstrating that the peptidyl transferase reaction can exist catalyzed by constructed fragments of 23S rRNA in the total absence of whatever ribosomal protein. Thus, the fundamental reaction of protein synthesis is catalyzed by ribosomal RNA. Rather than existence the primary catalytic constituents of ribosomes, ribosomal proteins are now thought to facilitate proper folding of the rRNA and to enhance ribosome role by properly positioning the tRNAs.

The direct involvement of rRNA in the peptidyl transferase reaction has important evolutionary implications. RNAs are idea to have been the first self-replicating macromolecules (see Chapter one). This notion is strongly supported by the fact that ribozymes, such as RNase P and self-splicing introns, can catalyze reactions that involve RNA substrates. The role of rRNA in the formation of peptide bonds extends the catalytic activities of RNA beyond self-replication to direct involvement in protein synthesis. Additional studies indicate that the Tetrahymena rRNA ribozyme tin catalyze the zipper of amino acids to RNA, lending acceptance to the possibility that the original aminoacyl tRNA synthetases were RNAs rather than proteins. The power of RNA molecules to catalyze the reactions required for poly peptide synthesis as well as for cocky-replication may provide an important link for understanding the early evolution of cells.

The Organization of mRNAs and the Initiation of Translation

Although the mechanisms of poly peptide synthesis in prokaryotic and eukaryotic cells are like, there are also differences, particularly in the signals that make up one's mind the positions at which synthesis of a polypeptide chain is initiated on an mRNA template (Figure 7.6). Translation does not simply begin at the 5´ end of the mRNA; it starts at specific initiation sites. The 5´ final portions of both prokaryotic and eukaryotic mRNAs are therefore noncoding sequences, referred to as five´ untranslated regions. Eukaryotic mRNAs usually encode but a single polypeptide chain, but many prokaryotic mRNAs encode multiple polypeptides that are synthesized independently from distinct initiation sites. For case, the E. coli lac operon consists of 3 genes that are translated from the aforementioned mRNA (see Figure vi.viii). Messenger RNAs that encode multiple polypeptides are chosen polycistronic, whereas monocistronic mRNAs encode a unmarried polypeptide chain. Finally, both prokaryotic and eukaryotic mRNAs end in noncoding three´ untranslated regions.

Figure 7.vi

Prokaryotic and eukaryotic mRNAs. Both prokaryotic and eukaryotic mRNAs contain untranslated regions (UTRs) at their five´ and 3´ ends. Eukaryotic mRNAs also contain 5´ 7-methylguanosine (m⁷G) caps and 3´ poly-A tails. Prokaryotic (more...)

In both prokaryotic and eukaryotic cells, translation e'er initiates with the amino acrid methionine, ordinarily encoded by AUG. Alternative initiation codons, such as GUG, are used occasionally in bacteria, but when they occur at the beginning of a polypeptide chain, these codons direct the incorporation of methionine rather than of the amino acid they usually encode (GUG usually encodes valine). In most bacteria, protein synthesis is initiated with a modified methionine residue (N-formylmethionine), whereas unmodified methionines initiate poly peptide synthesis in eukaryotes (except in mitochondria and chloroplasts, whose ribosomes resemble those of bacteria).

The signals that identify initiation codons are different in prokaryotic and eukaryotic cells, consistent with the singled-out functions of polycistronic and monocistronic mRNAs (Figure seven.7). Initiation codons in bacterial mRNAs are preceded by a specific sequence (called a Polish-Delgarno sequence, after its discoverers) that aligns the mRNA on the ribosome for translation past base-pairing with a complementary sequence well-nigh the three´ terminus of 16S rRNA. This base-pairing interaction enables bacterial ribosomes to initiate translation not only at the v´ terminate of an mRNA but likewise at the internal initiation sites of polycistronic letters. In contrast, ribosomes recognize most eukaryotic mRNAs by binding to the 7-methylguanosine cap at their 5´ terminus (meet Figure 6.39). The ribosomes then scan downstream of the 5´ cap until they meet an AUG initiation codon. Sequences that surround AUGs affect the efficiency of initiation, so in many cases the first AUG in the mRNA is bypassed and translation initiates at an AUG farther downstream. However, eukaryotic mRNAs have no sequence equivalent to the Shine-Delgarno sequence of prokaryotic mRNAs. Translation of eukaryotic mRNAs is instead initiated at a site adamant by scanning from the 5´ terminus, consequent with their functions every bit monocistronic messages that encode only unmarried polypeptides.

Effigy 7.7

Signals for translation initiation. Initiation sites in prokaryotic mRNAs are characterized by a Shine-Delgarno sequence that precedes the AUG initiation codon. Base pairing betwixt the Shine-Delgarno sequence and a complementary sequence well-nigh the 3´ (more...)

The Process of Translation

Translation is generally divided into 3 stages: initiation, elongation, and termination (Figure 7.8). In both prokaryotes and eukaryotes the first step of the initiation phase is the binding of a specific initiator methionyl tRNA and the mRNA to the small ribosomal subunit. The large ribosomal subunit then joins the complex, forming a functional ribosome on which elongation of the polypeptide concatenation proceeds. A number of specific nonribosomal proteins are also required for the various stages of the translation procedure (Table 7.1).

The first translation pace in bacteria is the bounden of three initiation factors (IF-ane, IF-two, and IF-3) to the 30S ribosomal subunit (Effigy 7.9). The mRNA and initiator N-formylmethionyl tRNA and so join the complex, with IF-2 (which is bound to GTP) specifically recognizing the initiator tRNA. IF-3 is so released, allowing a 50S ribosomal subunit to associate with the complex. This association triggers the hydrolysis of GTP jump to IF-2, which leads to the release of IF-one and IF-2 (spring to Gross domestic product). The effect is the formation of a 70S initiation complex (with mRNA and initiator tRNA bound to the ribosome) that is ready to begin peptide bond formation during the elongation stage of translation.

Figure 7.nine

Initiation of translation in bacteria. 3 initiation factors (IF-1, IF-2, and IF-3) first bind to the 30S ribosomal subunit. This step is followed by binding of the mRNA and the initiator N-formylmethionyl (fMet) tRNA, which is recognized by IF-2 spring (more...)

Initiation in eukaryotes is more than complicated and requires at least ten proteins (each consisting of multiple polypeptide chains), which are designated eIFs (eastwardukaryotic initiation factors; see Table 7.one). The factors eIF-1, eIF-1A, and eIF-iii bind to the 40S ribosomal subunit, and eIF-2 (in a circuitous with GTP) associates with the initiator methionyl tRNA (Figure 7.10). The mRNA is recognized and brought to the ribosome past the eIF-4 group of factors. The 5´ cap of the mRNA is recognized by eIF-4E. Another factor, eIF-4G, binds to both eIF-4E and to a protein (poly-A binding protein or PABP) associated with the poly-A tail at the iii' end of the mRNA. Eukaryotic initiation factors thus recognize both the 5' and iii' ends of mRNAs, bookkeeping for the stimulatory effect of polyadenylation on translation. The initiation factors eIF-4E and eIF-4G, in association with eIF-4A and eIF-4B, then bring the mRNA to the 40S ribosomal subunit, with eIF-4G interacting with eIF-iii. The 40S ribosomal subunit, in association with the bound methionyl tRNA and eIFs, then scans the mRNA to identify the AUG initiation codon. When the AUG codon is reached, eIF-5 triggers the hydrolysis of GTP bound to eIF-2. Initiation factors (including eIF-2 leap to Gross domestic product) are then released, and a 60S subunit binds to the 40S subunit to form the 80S initiation complex of eukaryotic cells.

Effigy vii.10

Initiation of translation in eukaryotic cells. Initiation factors eIF-three, eIF-ane, and eIF-1A bind to the 40S ribosomal subunit. The initiator methionyl tRNA is brought to the ribosome past eIF-2 (complexed to GTP), and the mRNA by eIF-4E (which binds to the (more than...)

Afterward the initiation complex has formed, translation gain by elongation of the polypeptide chain. The mechanism of elongation in prokaryotic and eukaryotic cells is very similar (Figure 7.11). The ribosome has iii sites for tRNA binding, designated the P (peptidyl), A (aminoacyl), and E (get out) sites. The initiator methionyl tRNA is bound at the P site. The outset stride in elongation is the bounden of the side by side aminoacyl tRNA to the A site by pairing with the 2d codon of the mRNA. The aminoacyl tRNA is escorted to the ribosome past an elongation factor (EF-Tu in prokaryotes, eEF-1α in eukaryotes), which is complexed to GTP. The GTP is hydrolyzed to Gross domestic product as the correct aminoacyl tRNA is inserted into the A site of the ribosome and the elongation factor bound to Gdp is released. The requirement for hydrolysis of GTP before EF-Tu or eEF-1α is released from the ribosome is the rate-limiting step in elongation and provides a fourth dimension interval during which an wrong aminoacyl tRNA, which would bind less strongly to the mRNA codon, can dissociate from the ribosome rather than being used for protein synthesis. Thus, the expenditure of a high-energy GTP at this step is an of import contribution to accurate protein synthesis; it allows time for proofreading of the codon-anticodon pairing before the peptide bond forms.

Figure seven.11

Elongation phase of translation. The ribosome has 3 tRNA-binding sites, designated P (peptidyl), A (aminoacyl), and Eastward (exit). The initiating N-formylmethionyl tRNA is positioned in the P site, leaving an empty A site. The second aminoacyl tRNA (e.g., (more...)

In one case EF-Tu (or eEF-1α) has left the ribosome, a peptide bond can exist formed between the initiator methionyl tRNA at the P site and the 2d aminoacyl tRNA at the A site. This reaction is catalyzed by the large ribosomal subunit, with the rRNA playing a critical role (as already discussed). The outcome is the transfer of methionine to the aminoacyl tRNA at the A site of the ribosome, forming a peptidyl tRNA at this position and leaving the uncharged initiator tRNA at the P site. The side by side footstep in elongation is translocation, which requires another elongation factor (EF-G in prokaryotes, eEF-two in eukaryotes) and is again coupled to GTP hydrolysis. During translocation, the ribosome moves three nucleotides along the mRNA, positioning the next codon in an empty A site. This stride translocates the peptidyl tRNA from the A site to the P site, and the uncharged tRNA from the P site to the E site. The ribosome is so left with a peptidyl tRNA bound at the P site, and an empty A site. The binding of a new aminoacyl tRNA to the A site so induces the release of the uncharged tRNA from the E site, leaving the ribosome set for insertion of the next amino acid in the growing polypeptide chain.

As elongation continues, the EF-Tu (or eEF-1α) that is released from the ribosome bound to GDP must be reconverted to its GTP class (Figure 7.12). This conversion requires a third elongation gene, EF-Ts (eEF-1βγ in eukaryotes), which binds to the EF-Tu/Gross domestic product complex and promotes the exchange of bound Gdp for GTP. This commutation results in the regeneration of EF-Tu/GTP, which is now ready to escort a new aminoacyl tRNA to the A site of the ribosome, commencement a new wheel of elongation. The regulation of EF-Tu by GTP binding and hydrolysis illustrates a mutual means of the regulation of protein activities. Equally will be discussed in later chapters, similar mechanisms control the activities of a wide multifariousness of proteins involved in the regulation of prison cell growth and differentiation, likewise as in protein transport and secretion.

Figure vii.12

Regeneration of EF-Tu/GTP. EF-Tu complexed to GTP escorts the aminoacyl tRNA to the ribosome. The leap GTP is hydrolyzed as the correct tRNA is inserted, so EF-Tu complexed to Gdp is released. The EF-Tu/GDP complex is inactive and unable to demark another (more...)

Elongation of the polypeptide chain continues until a end codon (UAA, UAG, or UGA) is translocated into the A site of the ribosome. Cells do non incorporate tRNAs with anticodons complementary to these termination signals; instead, they take release factors that recognize the signals and terminate protein synthesis (Effigy 7.thirteen). Prokaryotic cells contain ii release factors that recognize termination codons: RF-1 recognizes UAA or UAG, and RF-2 recognizes UAA or UGA (see Table 7.1). In eukaryotic cells a unmarried release factor (eRF-1) recognizes all three termination codons. Both prokaryotic and eukaryotic cells also contain release factors (RF-three and eRF-3, respectively) that practice not recognize specific termination codons but act together with RF-1 (or eRF-one) and RF-2. The release factors demark to a termination codon at the A site and stimulate hydrolysis of the bond between the tRNA and the polypeptide concatenation at the P site, resulting in release of the completed polypeptide from the ribosome. The tRNA is then released, and the ribosomal subunits and the mRNA template dissociate.

Figure 7.13

Termination of translation. A termination codon (e.g., UAA) at the A site is recognized past a release factor rather than past a tRNA. The result is the release of the completed polypeptide chain, followed by the dissociation of tRNA and mRNA from the ribosome. (more...)

Messenger RNAs tin be translated simultaneously by several ribosomes in both prokaryotic and eukaryotic cells. In one case one ribosome has moved away from the initiation site, another tin bind to the mRNA and begin synthesis of a new polypeptide chain. Thus, mRNAs are usually translated by a series of ribosomes, spaced at intervals of near 100 to 200 nucleotides (Figure vii.14). The grouping of ribosomes bound to an mRNA molecule is called a polyribosome, or polysome. Each ribosome within the group functions independently to synthesize a divide polypeptide chain.

Effigy seven.14

Polysomes. Messenger RNAs are translated by a series of multiple ribosomes (a polysome). (A) Electron micrograph of a eukaryotic polysome. (B) Schematic of a generalized poly-some. Note that the ribosomes closer to the 3´ end of the mRNA have (more than...)

Regulation of Translation

Although transcription is the primary level at which gene expression is controlled, the translation of mRNAs is likewise regulated in both prokaryotic and eukaryotic cells. One mechanism of translational regulation is the bounden of repressor proteins, which block translation, to specific mRNA sequences. The all-time understood case of this machinery in eukaryotic cells is regulation of the synthesis of ferritin, a poly peptide that stores iron within the jail cell. The translation of ferritin mRNA is regulated by the supply of iron: More ferritin is synthesized if iron is abundant (Figure seven.15). This regulation is mediated by a protein which (in the absenteeism of iron) binds to a sequence (the iron response element, or IRE) in the 5´ untranslated region of ferritin mRNA, blocking its translation. In the presence of iron, the repressor no longer binds to the IRE and ferritin translation is able to go on.

Figure 7.15

Translational regulation of ferritin. The mRNA contains an atomic number 26 response chemical element (IRE) near its 5´ cap. In the presence of adequate supplies of iron, translation of the mRNA proceeds normally. If iron is scarce, all the same, a poly peptide (called the (more than...)

Information technology is interesting to annotation that the regulation of translation of ferritin mRNA past atomic number 26 is similar to the regulation of transferrin receptor mRNA stability, which was discussed in the previous chapter (come across Figure six.48). Namely, the stability of transferrin receptor mRNA is regulated by protein bounden to an IRE in its 3´ untranslated region. The same protein binds to the IREs of both ferritin and transferrin receptor mRNAs. Yet, the consequences of poly peptide bounden to the two IREs are quite dissimilar. Protein bound to the transferrin receptor IRE protects the mRNA from deposition rather than inhibiting its translation. These distinct effects presumably result from the unlike locations of the IRE in the 2 mRNAs. To function as a repressor-bounden site, the IRE must be located within 70 nucleotides of the 5´ cap of ferritin mRNA, suggesting that poly peptide binding to the IRE blocks translation past interfering with cap recognition and binding of the 40S ribosomal subunit. Rather than inhibiting translation, poly peptide binding to the same sequence in the 3´ untranslated region of transferrin receptor mRNA protects the mRNA from nuclease degradation. Binding of the same regulatory poly peptide to different sites on mRNA molecules can thus have distinct furnishings on gene expression, in one case inhibiting translation and in the other stabilizing the mRNA to increase protein synthesis.

Some other machinery of translational regulation in eukaryotic cells, resulting in global effects on overall translational action rather than on the translation of specific mRNAs, involves modulation of the activity of initiation factors, particularly eIF-ii. Equally already discussed, eIF-2 (complexed with GTP) binds to the initiator methionyl tRNA, bringing it to the ribosome. The subsequent release of eIF-2 is accompanied by GTP hydrolysis, leaving eIF-2 as an inactive GDP circuitous. To participate in another bike of initiation, the eIF-ii/GTP circuitous must be regenerated by the commutation of bound Gross domestic product for GTP. This exchange is mediated by another gene, eIF-2B. The control of eIF-2 activity past GTP bounden and hydrolysis is thus similar to that of EF-Tu (see Effigy 7.12). However, the regulation of eIF-2 provides a disquisitional control betoken in a variety of eukaryotic cells. In particular, eIF-ii tin can exist phosphorylated by regulatory protein kinases. This phosphorylation blocks the substitution of bound Gross domestic product for GTP, thereby inhibiting initiation of translation. 1 type of prison cell in which such phosphorylation occurs is the reticulocyte, which is devoted to the synthesis of hemoglobin (Figure 7.16). The translation of globin mRNA is controlled by the availability of heme: The mRNA is translated simply if acceptable heme is available to grade functional hemoglobin molecules. In the absenteeism of heme, a poly peptide kinase that phosphorylates eIF-2 is activated, and farther translation is inhibited. Similar mechanisms have been establish to control protein synthesis in other cell types, specially virus-infected cells in which viral protein synthesis is inhibited by interferon.

Effigy vii.16

Regulation of translation by phosphorylation of eIF-2. Translation in reticulocytes (which is devoted to synthesis of hemoglobin) is controlled by the supply of heme, which regulates the activity of eIF-2. The active form of eIF-2 (complexed with GTP) (more...)

Other studies have implicated eIF-4E, which binds to the five´ cap of mRNAs, as a translational regulatory poly peptide. For example, the hormone insulin stimulates protein synthesis in adipocytes and muscle cells. This effect of insulin is mediated, at least in role, by phosphorylation of proteins associated with eIF-4E, resulting in stimulation of eIF-4E action and increased rates of translational initiation.

Translational regulation is particularly of import during early on development. As discussed in Chapter vi, a variety of mRNAs are stored in oocytes in an untranslated grade; the translation of these stored mRNAs is activated at fertilization or later stages of evolution. 1 mechanism of such translational regulation is the controlled polyadenylation of oocyte mRNAs. Many untranslated mRNAs are stored in oocytes with short poly-A tails (approximately 20 nucleotides). These stored mRNAs are subsequently recruited for translation at the appropriate stage of evolution by the lengthening of their poly-A tails to several hundred nucleotides. In add-on, the translation of some mRNAs during development appears to be regulated by repressor proteins that bind to specific sequences in their three´ untranslated regions. These regulatory proteins may also direct mRNAs to specific regions of eggs or embryos, allowing localized synthesis of the encoded proteins during embryonic development.

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Cardinal Experiment: Catalytic Office of Ribosomal RNA.

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Molecular Medicine: Antibiotics and Protein Synthesis.

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Source: https://www.ncbi.nlm.nih.gov/books/NBK9849/

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