Lodish H. - Molecular Cell Biology (5ed, Freeman, 2003) (794361), страница 52
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Thisprecise linear array of ribonucleotides in groups of three inmRNA specifies the precise linear sequence of amino acids ina polypeptide chain and also signals where synthesis of thechain starts and stops.Because the genetic code is a comma-less, non-overlappingtriplet code, a particular mRNA theoretically could be translated in three different reading frames. Indeed some mRNAshave been shown to contain overlapping information that canbe translated in different reading frames, yielding differentpolypeptides (Figure 4-20). The vast majority of mRNAs,however, can be read in only one frame because stop codonsencountered in the other two possible reading frames terminate translation before a functional protein is produced.
Another unusual coding arrangement occurs because of frame-4.4 • The Three Roles of RNA in TranslationFrame 15GCU UGU UUA CGA AUU AAlaCysLeuArgIlemRNAPolypeptideFrame 25G CUU GUU UAC GAA UUALeuValTyrGluLeu▲ FIGURE 4-20 Example of how the genetic code—anon-overlapping, comma-less triplet code—can be read indifferent frames.
If translation of the mRNA sequence shownbegins at two different upstream start sites (not shown), thentwo overlapping reading frames are possible. In this example,the codons are shifted one base to the right in the lower frame.As a result, the same nucleotide sequence specifies differentamino acids during translation. Although they are rare, manyinstances of such overlaps have been discovered in viral andcellular genes of prokaryotes and eukaryotes.
It is theoreticallypossible for the mRNA to have a third reading frame.shifting. In this case the protein-synthesizing machinery mayread four nucleotides as one amino acid and then continuereading triplets, or it may back up one base and read all succeeding triplets in the new frame until termination of the chainoccurs.
These frameshifts are not common events, but a fewdozen such instances are known.The meaning of each codon is the same in most knownorganisms—a strong argument that life on earth evolvedonly once. However, the genetic code has been found to differ for a few codons in many mitochondria, in ciliated protozoans, and in Acetabularia, a single-celled plant.
As shownin Table 4-2, most of these changes involve reading of normal stop codons as amino acids, not an exchange of oneamino acid for another. These exceptions to the general codeprobably were later evolutionary developments; that is, at nosingle time was the code immutably fixed, although massivechanges were not tolerated once a general code began tofunction early in evolution.121The Folded Structure of tRNA PromotesIts Decoding FunctionsTranslation, or decoding, of the four-nucleotide language ofDNA and mRNA into the 20–amino acid language of proteins requires tRNAs and enzymes called aminoacyl-tRNAsynthetases. To participate in protein synthesis, a tRNA molecule must become chemically linked to a particular aminoacid via a high-energy bond, forming an aminoacyl-tRNA;the anticodon in the tRNA then base-pairs with a codon inmRNA so that the activated amino acid can be added to thegrowing polypeptide chain (Figure 4-21).Some 30–40 different tRNAs have been identified inbacterial cells and as many as 50–100 in animal and plantcells.
Thus the number of tRNAs in most cells is morethan the number of amino acids used in protein synthesis(20) and also differs from the number of amino acidcodons in the genetic code (61). Consequently, manyamino acids have more than one tRNA to which they canattach (explaining how there can be more tRNAs thanamino acids); in addition, many tRNAs can pair withmore than one codon (explaining how there can be morecodons than tRNAs).The function of tRNA molecules, which are 70–80 nucleotides long, depends on their precise three-dimensionalstructures.
In solution, all tRNA molecules fold into a similar stem-loop arrangement that resembles a cloverleaf whendrawn in two dimensions (Figure 4-22a). The four stems areshort double helices stabilized by Watson-Crick base pairing;three of the four stems have loops containing seven or eightbases at their ends, while the remaining, unlooped stem contains the free 3 and 5 ends of the chain. The three nucleotides composing the anticodon are located at the centerof the middle loop, in an accessible position that facilitatescodon-anticodon base pairing. In all tRNAs, the 3 end ofthe unlooped amino acid acceptor stem has the sequenceCCA, which in most cases is added after synthesis and processing of the tRNA are complete. Several bases in mosttRNAs also are modified after synthesis.
Viewed in threeTABLE 4-2 Known Deviations from the Universal Genetic CodeCodonUniversalCodeUnusualCode*OccurrenceUGAStopTrpMycoplasma, Spiroplasma, mitochondria of many speciesCUGLeuThrMitochondria in yeastsUAA, UAGStopGlnAcetabularia, Tetrahymena, Paramecium, etc.UGAStopCysEuplotes*“Unusual code” is used in nuclear genes of the listed organisms and in mitochondrial genes as indicated.SOURCE: S. Osawa et al., 1992, Microbiol. Rev. 56:229.122CHAPTER 4 • Basic Molecular Genetic MechanismsAmino acid(Phe)H OH2NCCH2CHigh-energyester bondOHH2NOHHOCCOH2NCH212OCH2Net result:Phe is selectedby its codon5AAAUUUmRNA3corresponding tRNA.
Step 2 : A three-base sequence in thetRNA (the anticodon) then base-pairs with a codon in the mRNAspecifying the attached amino acid. If an error occurs in eitherstep, the wrong amino acid may be incorporated into apolypeptide chain. Phe phenylalanine.nucleic acid sequences in mRNA into amino acid sequencesin proteins. Step 1 : An aminoacyl-tRNA synthetase first couplesa specific amino acid, via a high-energy ester bond (yellow), toeither the 2 or 3 hydroxyl of the terminal adenosine in theamino acid.
As noted above, however, many cells containfewer than 61 tRNAs. The explanation for the smaller numberlies in the capability of a single tRNA anticodon to recognizemore than one, but not necessarily every, codon correspondingto a given amino acid. This broader recognition can occur because of nonstandard pairing between bases in the so-calledwobble position: that is, the third (3) base in an mRNA codonand the corresponding first (5) base in its tRNA anticodon.The first and second bases of a codon almost alwaysform standard Watson-Crick base pairs with the third anddimensions, the folded tRNA molecule has an L shape withthe anticodon loop and acceptor stem forming the ends ofthe two arms (Figure 4-22b).Nonstandard Base Pairing Often Occurs BetweenCodons and AnticodonsIf perfect Watson-Crick base pairing were demanded betweencodons and anticodons, cells would have to contain exactly 61different tRNA species, one for each codon that specifies an3(a)Science 147:1462; part (b) from J.
G. Arnez andD. Moras, 1997, Trends Biochem. Sci. 22:211.]CAAAAminoacyl-tRNA▲ FIGURE 4-21 Two-step decoding process for translating(a) Although the exact nucleotide sequencevaries among tRNAs, they all fold into fourbase-paired stems and three loops. The CCAsequence at the 3 end also is found in alltRNAs. Attachment of an amino acid to the 3A yields an aminoacyl-tRNA. Some of the A,C, G, and U residues are modified in mosttRNAs (see key).
Dihydrouridine (D) is nearlyalways present in the D loop; likewise,ribothymidine (T) and pseudouridine () arealmost always present in the TCG loop.Yeast alanine tRNA, represented here, alsocontains other modified bases. The triplet atthe tip of the anticodon loop base-pairs withthe corresponding codon in mRNA. (b) Threedimensional model of the generalized backbone of all tRNAs. Note the L shape of themolecule. [Part (a) see R. W.
Holly et al., 1965,CAMP+ PPiAAAAminoacyltRNA synthetase tRNA specific forspecific for PhePhe (tRNAPhe) FIGURE 4-22 Structure of tRNAs.OtRNAPhe bindsto the UUU codonLinkage ofPhe to tRNAPheATPHD = dihydrouridineI = inosineT = ribothymidine = pseudouridinem = methyl groupD loopDG AmGUU G C GCGG C G CG D Am2GAnticodon loopCUCCCUU 1IACC5 AAcceptorGCstemGCGUCGGCTCGloopUUGCU UAA G G C CGU C C G GCT GA CAG DG VariableGGloopG2Gml3CAnticodonC C G3321mRNA5Codon(b)TCG loopAcceptor stemC5CD loopVariableloopAnticodon loopA34.4 • The Three Roles of RNA in Translationsecond bases, respectively, of the corresponding anticodon,but four nonstandard interactions can occur between basesin the wobble position.
Particularly important is the G·Ubase pair, which structurally fits almost as well as the standard G·C pair. Thus, a given anticodon in tRNA with G inthe first (wobble) position can base-pair with the two corresponding codons that have either pyrimidine (C or U) in thethird position (Figure 4-23). For example, the phenylalaninecodons UUU and UUC (5n3) are both recognized by thetRNA that has GAA (5n3) as the anticodon. In fact, anytwo codons of the type NNPyr (N any base; Pyr pyrimidine) encode a single amino acid and are decoded bya single tRNA with G in the first (wobble) position of theanticodon.Although adenine rarely is found in the anticodon wobbleposition, many tRNAs in plants and animals contain inosinetRNA35If these bases are infirst, or wobble, position ofanticodon3 21CAGUI1235 mRNA 3GUCUAGCAU5 mRNA 31233 21then the tRNA mayrecognize codons inmRNA having thesebases in third positionIf these bases are inthird, or wobble, positionof codon of an mRNAC A G UGIUICUAGIthen the codon maybe recognized by atRNA having thesebases in first positionof anticodon53tRNA▲ FIGURE 4-23 Nonstandard codon-anticodon base pairingat the wobble position.
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