Translation

Messenger RNA molecules are an intermediate step in the decoding of genes; they must next be translated into protein products. The machinery that translates mRNAs is quite complicated, and it took many years to unravel the mystery of their functioning. Proteins are polymers of twenty different amino acids arranged in a particular sequence. This is true of proteins from viruses to human beings. Hundreds of thousands of different proteins exist in the living world. They differ by the arrangement and length of amino acids (table 4.1). The central question then is this: how does the translation machinery "know" where to insert a given amino acid in a growing protein molecule and how does it "know" where to start and where to stop the synthesis of a particular protein? This is done by the cellular decoding machinery that translates the sequence of nucleotides in mRNA into a sequence of amino acids.

Each amino acid is coded for in DNA by a sequence of three adjacent base pairs. A set of three contiguous base pairs is called a "codon." For example, ATG determines the amino acid methionine. Most amino acids are coded for by several codons: for example, both AAA and AAG code for lysine. Some amino acids are coded for by as many as six different codons. Interestingly, three codons, TAA, TAG, and TGA do not correspond to any amino acids; they mean "stop" and instruct the translation machinery to stop making a protein molecule.

Figure 4.4 Transcription. A. The gene in the DNA has a region known as the promoter that signals the RNA polymerase to bind to the DNA and begin making RNA using nucleotide subunits. DNA is diagrammed as a double helix, with the strand that is read printed darker than the opposite strand. The gene also has a terminator region that signals the end of the gene. B. The process of transcription. In Step 1, RNA polymerase binds to the promoter. Step 2 shows the initiation of mRNA production. Step 3 shows a long piece of mRNA, attached to the RNA polymerase, towards the end of the process. Transcription ends in Step 4 when the RNA polymerase finds the terminator and falls off the DNA.

Figure 4.4 Transcription. A. The gene in the DNA has a region known as the promoter that signals the RNA polymerase to bind to the DNA and begin making RNA using nucleotide subunits. DNA is diagrammed as a double helix, with the strand that is read printed darker than the opposite strand. The gene also has a terminator region that signals the end of the gene. B. The process of transcription. In Step 1, RNA polymerase binds to the promoter. Step 2 shows the initiation of mRNA production. Step 3 shows a long piece of mRNA, attached to the RNA polymerase, towards the end of the process. Transcription ends in Step 4 when the RNA polymerase finds the terminator and falls off the DNA.

Table 4.1 Examples of Proteins a nd Their Amino Acid Compositions

Amino acid

(abbrev)

Hemoglobin

polymerase

Insulin

Fibrillin

Rubisco

Alanine

(A)

19

91

1

96

44

Arginine

(R)

8

76

1

131

29

Asparagine

(N)

1

12

3

188

16

Aspartic acid

(D)

8

42

0

173

26

Cysteine

(C)

2

0

6

361

9

Glutamine

(Q)

5

16

3

101

11

Glutamic acid

(E)

5

87

4

201

32

Glycine

(G)

6

58

4

307

46

Histidine

(H)

8

18

2

48

14

Isoleucine

(I)

1

25

2

148

22

Leucine

(L)

25

124

6

141

40

Lysine

(K)

5

42

1

111

23

Methionine

(M)

0

16

0

52

9

Phenylalanine

(F)

6

27

3

84

22

Proline

(P)

6

48

1

175

20

Serine

(S)

15

31

3

173

17

Threonine

(T)

6

30

3

166

28

Tryptophan

(W)

1

14

0

13

8

Tyrosine

(Y)

4

24

4

94

17

Valine

(V)

10

51

4

18

32

total #aa

141

832

51

2781

465

Compositions are for:

Human P-hemoglobin, the protein responsible for carrying oxygen in our blood. This is the protein that is mutated in sickle-cell anemia.

DNA polymerase from Thermus aquaticus used in PCR reactions.

Human insulin, the protein necessary for regulating blood sugar.

Human fibrillin, a connective tissue protein, which if mutated can cause Marfan's syndrome.

Rubisco (ribulose bisphosphate carboxylase), which is the most abundant protein in the world and necessary for all of life. It is present in all plants and is used to convert the energy from the sun to fix carbon; that is, to make carbon available to nonplants. This is the composition of rubisco from sugar maple.

You may already have guessed that stop codons are found at the end of a gene. In addition, there is a single "start" codon, ATG, that, we just saw, codes for methionine. Does this mean that all proteins start with the amino acid methionine? The answer is yes, with very few exceptions. However, many proteins are processed further after they are made, and, sometimes, this process involves removing some amino acids at the beginning of the protein. This is the case for both hemoglobin and insulin listed in table 4.1.

ATG AGG GGG CTG CC ATGT C CC CAG AG AGC A G TG TTG GGC CTG AGC ATG GC AGGG TG A..

1V3130 033 0V0001V0V0000101013010VO WO3300V01001V0 001000 V31

Corresponding mRNA

Corresponding protein (using singie-ietter abbreviations)

Figure 4.5 Converting a Gene to a Phenotype. A. A short stretch of double-stranded DNA. B. The corresponding mRNA. C. The corresponding protein made using this gene.

Figure 4.5 shows a hypothetical very short gene (the DNA double helix), its mRNA copy (where U replaces T), and the protein product of that gene. The gene has an ATG codon at the beginning, and one of the stop codons (TGA) at the end. Note that all the codons (except TGA) direct that a particular amino acid be placed in a particular position in the protein. The codes for all twenty amino acids and the "start" and "stop" codons are known (figure 4.6), and these are called the genetic code. The genetic code is universal (with very minor exceptions), a fact that led James Watson to claim that "what's true for E. coli [a bacterium] is true for an elephant."

At this point, let us examine in greater detail the process of translation. To understand this mechanism, it is useful to think in terms of two different languages. In that sense, both DNA and RNA "speak" a language where the "words" are codons made up of three bases. RNA "speaks" almost the same language as DNA; let us call it a "dialect" where U replaces T. The DNA language and the RNA dialect are in fact indistinguishable because U and T have the same "meaning." However, proteins do not "speak" the base language or dialect: they speak the language of amino acids. How is one language (and its dialect) translated into the other? In human affairs, an interpreter does the job. Does it work the same way in living cells? Yes, it does.

First position

Second position

Third position

U

C

A

G

U

UUU Phe UUC Phe LI U A Leu UUG Leu.

F [L

UCU Ser1 UCC Ser U C A Ser UCG Serj

U A U Tyr' U A C Tyr.

Y

U G U Cys UGC Cys J

k

C A G

U A A Stop U AG Stop

111 G A Stop] UGG Trp W

C

CUU Leu1 CUC Leu CUA Leu CUG Leuj

CCU Ser' CCC Ser CCA Ser CCG Ser,

CAU His CAC His. CAA Gin' C AG Gin .

CGG Arg j

C A G

A

A u U He 1 AUC ILe AU A ILe

M

ACL) Thr' ACC Thr AC A Thr ACG Thr,

A A U Aspl AAC Asp J AAA Lysl|* A A G Lys J

AGU Ser A G C Ser, AG A Arg" AG G Arg.

S [R

C A G

|AUG Met|

G

G U U Val1 GUC Val GUA VaL G U G Val j

GCU Ala1 GCC Ala G C A Ala GCG Ala,

A

GAU Asp G A C Asp G A A Glu GAG Glu

D E

GGU Gly1 GGC Gty G G A Gly GGG Gly j

U C A G

Figure 4.6 The Genetic Code. Note that amino acids can be coded for by several codons. Special codons for start and stop are shown in dark boxes.

Figure 4.6 The Genetic Code. Note that amino acids can be coded for by several codons. Special codons for start and stop are shown in dark boxes.

In the early 1960s, researchers discovered a class of small RNA molecules, called transfer RNAs (tRNAs), that have the ability to bind specific amino acids. What's more, it was realized that these tRNAs also had the ability to "recognize" mRNA codons via three complementary bases that they possess in what is called an anticodon. Therefore, these tRNAs can communicate with both the "base language" (thanks to their anticodons) and the "protein language" (thanks to their ability to bind amino acids). What happens (figure 4.7) is that tRNAs loaded with their amino acids line up along an mRNA molecule, interact through their anticodons with specific mRNA codons, and, by doing so, bring the amino acids they carry into very close contact. These amino acids can then form chemical bonds between one another and so produce a protein.

The "assembly line" containing the mRNA, tRNAs, and a growing protein needs to be held together in a precise fashion to function sugar (ribosc) - phosphate backbone of mRNA

niRNA

\ U GAGGGGGC UGCCAUGU

codons anticodons

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook


Post a comment