H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003) (796244), страница 50
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Transfer RNA (tRNA) is the key to deciphering thecodons in mRNA. Each type of amino acid has its ownsubset of tRNAs, which bind the amino acid and carry itto the growing end of a polypeptide chain if the next codonin the mRNA calls for it. The correct tRNA with its attachedamino acid is selected at each step because each specifictRNA molecule contains a three-nucleotide sequence, ananticodon, that can base-pair with its complementary codonin the mRNA.3.
Ribosomal RNA (rRNA) associates with a set ofproteins to form ribosomes. These complex structures,which physically move along an mRNA molecule, catalyzethe assembly of amino acids into polypeptide chains. Theyalso bind tRNAs and various accessory proteins necessaryfor protein synthesis. Ribosomes are composed of a largeand a small subunit, each of which contains its own rRNAmolecule or molecules.H HN C R6mRNACCOC O H C OOOtRNA4leaving54.4 The Three Roles of RNAin TranslationR5aa7-tRNA7arriving HH2N CR7C OC AGCU U U A G CG G G A A A U C G G U C3Codon Codon Codon Codon Codon Codon Codonaa1aa2aa3aa4aa5aa6aa7Movement of ribosome▲ FIGURE 4-19 The three roles of RNA in proteinsynthesis.
Messenger RNA (mRNA) is translated into proteinby the joint action of transfer RNA (tRNA) and the ribosome,which is composed of numerous proteins and two majorribosomal RNA (rRNA) molecules (not shown). Note the basepairing between tRNA anticodons and complementary codonsin the mRNA. Formation of a peptide bond between the aminogroup N on the incoming aa-tRNA and the carboxyl-terminal Con the growing protein chain (purple) is catalyzed by one of therRNAs.
aa amino acid; R side group. [Adapted fromA. J. F. Griffiths et al., 1999, Modern Genetic Analysis, W. H. Freemanand Company.]These three types of RNA participate in translation in allcells. Indeed, development of three functionally distinctRNAs was probably the molecular key to the origin of life.How the structure of each RNA relates to its specific task isdescribed in this section; how the three types work together,along with required protein factors, to synthesize proteins isdetailed in the following section. Since translation is essentialfor protein synthesis, the two processes commonly are referred to interchangeably.
However, the polypeptide chainsresulting from translation undergo post-translational foldingand often other changes (e.g., chemical modifications, association with other chains) that are required for production ofmature, functional proteins (Chapter 3).Messenger RNA Carries Information from DNAin a Three-Letter Genetic CodeAs noted above, the genetic code used by cells is a tripletcode, with every three-nucleotide sequence, or codon, being“read” from a specified starting point in the mRNA. Of the64 possible codons in the genetic code, 61 specify individualamino acids and three are stop codons.
Table 4-1 shows thatmost amino acids are encoded by more than one codon.Only two—methionine and tryptophan—have a single120CHAPTER 4 • Basic Molecular Genetic MechanismsTABLE 4-1 The Genetic Code (RNA to Amino Acids)*FirstPosition(5 end)ThirdPosition(3 end)Second PositionUCAGPhePheSerSerTyrTyrCysCysUCLeuLeuSerSerStopStopStopTrpAGLeuLeuProProHisHisArgArgUCLeuLeu (Met)*ProProGlnGlnArgArgAGIleIleThrThrAsnAsnSerSerUCIleMet (start)ThrThrLysLysArgArgAGValValAlaAlaAspAspGlyGlyUCValVal (Met)*AlaAlaGluGluGlyGlyAGUCAG*AUG is the most common initiator codon; GUG usually codes for valine, and CUG for leucine, but, rarely,these codons can also code for methionine to initiate a protein chain.codon; at the other extreme, leucine, serine, and arginine areeach specified by six different codons. The different codonsfor a given amino acid are said to be synonymous.
The codeitself is termed degenerate, meaning that more than onecodon can specify the same amino acid.Synthesis of all polypeptide chains in prokaryotic and eukaryotic cells begins with the amino acid methionine. In mostmRNAs, the start (initiator) codon specifying this aminoterminal methionine is AUG.
In a few bacterial mRNAs,GUG is used as the initiator codon, and CUG occasionallyis used as an initiator codon for methionine in eukaryotes.The three codons UAA, UGA, and UAG do not specifyamino acids but constitute stop (termination) codons thatmark the carboxyl terminus of polypeptide chains in almostall cells. The sequence of codons that runs from a specificstart codon to a stop codon is called a reading frame. 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.
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