Bio 2.3.PDF

Chapter 2: G*ne Hxpression L*sscn 2.3 Translation Introduction The process of transcription (described in Lesson 2.2) involves using DNA as a template to transcribe a copy of the genetic code in the form of messenger RNA (mRNA), a similar molecule. This process is not overly complex because the t...

Chapter 2: G*ne Hxpression L*sscn 2.3 Translation Introduction The process of transcription (described in Lesson 2.2) involves using DNA as a template to transcribe a copy of the genetic code in the form of messenger RNA (mRNA), a similar molecule. This process is not overly complex because the two molecules (DNA and mRNA) are both nucleic acids, and complementary base pairing is an efficient and naturalway to transfer the information from a DNA molecule into mRNA form. Translation is a more complex enterprise, by which the information encoded in mRNA (a nucleic acid) must be transformed into a completely different type of macromolecule (a protein). This lesson details the mechanism by which translation is carried out by a ribosome and how mutations or changes in the genetic code may result in changes to the protein that is produced. 2.3.01 lnterpreting the Genetic Code As established in Lesson 1.1 , nucleotides are the building blocks of nucleic acids (ie, DNA and RNA), and there are four types of nucleotides in RNA (A, G, C, and U). The building blocks of proteins are amino acids, of which there are ?"0 different types. In translation, a cell converts genetic information encoded within the nucleotide sequence into a protein. Because there are 20 tyies of amino acids in proteins and only four types of nucleotides in mRNA, the code cannot read as 1:1 (one nucleotide specifying one amino acid). Rather, a combination of three nucleotides (termed a codon) sppcifies a particular amino acid in the protein. A codon table can be used to determine which amino acid a particular codon specifies, as shown in Figure 2.1 1. Therefore, translation is the process by which the order of nucleotides (in the form of codons) in the mRNA transcript specifies the order in which amino acids are added to the growing protein chain. During translation, each codon in the mRNA transcript is read by the translation machinery in the 5' ) 3' direction. Second base in codon CA UUUI -. ucu I UAUI -rYr uucltn" ucct- uAcI U331"^ UUAI ucn is"t. UAA Stop UGA Stop uuclt"' UCGJ UAC Stop UGG Trp tr cuul ccu I cGUl tto nttnl cun teu 999 f t'o 3l3l "- cccl. cGA o f rArs 'a CUGJ cncIt'n o AUUI Acu AGU o I ll AUc il81o" AGC Ser i lle ncn AAAI E lt AUAJ f'nt.. ^^>LVS AGA Arg nucffin AGG GUUI Gcul GAULA"^ GGU GUC|... u"' GCCI ^. A'a UAUJ UUV cuR I ccn f GM'] ^, GGA GUGJ gAUl ^^^l(Jlu U99 Figure 2.11 The codon table for mRNA. 2.7  Chapter 2: Gene Hxpression As codons are read by translation machinery in groups of three, it is crucial that the correct groups of three are used to decode the information in the mRNA transcript. The translation machinery recognizes and begins translation at a specific set of three nucleotides (AUG) known as the start codon. Starting translation with a defined start codon ensures that the translation machinery sets the correct reading frame, as illustrated in Figure 2.12. mRNA sequence I 5'GCGUGUCAUCGGCA 3' i , Codon 1 Coclon ! Codon 3 Cfldofi 4 Reading frame 1 5'GO,S- rU'6g CflU CGd cA 3' + Codon 1 Codoil ? Codon 3 {iodon 4 Reading frame 2 5'G CGU GUC AUC GGC A 3' + Codon 1 Cr:don 2 Codon 3 Ccdun 4 Reading frame 3 5i GC $itl$ It$A $Og S$Ai3' 4 t = beginning of reading frame. Figure 2.12 An mRNA sequence has three possible reading frames. Incorrect groupings of nucleotides can result in the formation of completely different proteins, similar to how incorrect gfroupings of letters change a sentence's meaning. For example, if read using the correct starting point, the statement, "the car was red" is a complete sentence with recognizable words. lf the statement is read in groups of three letters starting just one letter to the right, the statement becomes, "hec arw asr ed," whicl"i is no longer a coherent sentence. By always starting with the correct group of three nucleotides (ie, the start codon), the translation machinery ensures that the reading frame is accurate, and the correct protein is made. There must also be a way to specify when the translation machinery should stop attaching amino acids to the protein chain. Just as start codons designate where translation begins, stop codons (UGA, UAG, or UAA, see Figure 2.1 1) specify where translation ends. 2.3.02 Transfer RNA (tRNA) and Anticodons To convert information encoded in the mRNA into the correct sequence of amino acids in the protein, each codon (made up of three mRNA nucleotides) must correspond with a specific amino acid. The key to matching the correct amino acid with its specific codon is found in another type of RNA, called transfer RNA (tRNA). A IRNA molecule is a small, single-stranded RNA molecule that base pairs with itself to form a complex three-dimensional L-shaped structure, which is often depicted as a cloverleaf shape for simplicity. When folded, the 5'and 3'ends of the IRNA are both located near the same end of the molecule. At the opposite end of the molecule, a loop called the anticodon is formed. Figure 2.13 depicts both the cloverleaf and three-dimensional form of IRNA structure. 38  Chapter 2: Gene Expression tRl{A cloverleaf model IRNA3{model L-*il* loop t Figure 2.13 IRNA structure. The anticodon is a three-nucleotide sequence found in each tRNA which is complementary to a particular mRNA codon. Although multiple codons may correspond to the same amino acid (see Concept 2.3.01), each IRNA is pairedwith a specific amino acid based on the unique sequence of the tRNA's anticodon, For example, an mRNA loOon for the amino acid threonine is 5'-ACA-3'. The corresponding IRNA has the complementary anticodqrr 3'-UGU-5'and should always carry the amino acid threonine on its 3'end, as shown in Figure 2.14. The'tRNA molecule is the necessary link to "decode" or convert the information found in the nucleotide sequence of the mRNA, to specify the correct order of amino acids during translation. Figure 2.14 IRNA anticodons base pair with mRNA codons. 39  ChaPter 2: Sene ExPression pairing Nucleotides in the first or second position within a codon require traditional Watson-Crick base in the third position may undergo less stringent base with the IRNA anticodon. However, the nucleotide pairing in a non-Watson-Crick manner known as wobble pairing. For example, a tRNA with the anticodon 3'-UCA-5' can base pair with the mRNA codons 5'-AGU-3' and 5'-AGC-3', both of which code for the amino acid serine, as shown in Figure 2.15. *IRNAanticod* UCA uc A ti'"t]j t"