Central dogma of genetics

Lecture 4

The Central dogma of Genetics: conversion of DNA to Proteins

• When a gene is “Expressed” [activated] it undergoes two main process /steps:1. The primary/template strand of

dsDNA is converted into an RNA strand, or what is called mRNA (messanger RNA), in a process called transcription

2. The mRNA strand is then converted into an amino acid chain in a process called translation.

• The basic process is illustrated in Fig 1 Fig1: adaped from klug p. 241

Step 1: Transcription• The RNA polymerase {shown in yellow), that performs

the conversion, unwinds the double helix, moves in the 5’ to 3’ direction of the coding/primary strand,

• It uses the antisense strand to produce a complementary mRNA strand. Remember the complements are: A <-> T and G<->C

• This mRNA is a complement of the complement of the primary strand; in other words:

• if ATA is the primary sequence; its DNA compliment is TAT,

• However in mRNA a T (thymine) is replaced by U (uracil)

• Therefore the TAT on the complimentary strand becomes AUA on the mRNA strand

• The net effect is the mRNA is an exact copy of the primary DNA strand but T being replaced by U

Adapted from

DNA version of genetic code table

• In order for a DNA sequence to be converted to amino acid sequence and subsequently a protein a code is used.

• The code uses sets of 3, triplets, of nucleotides. Often called a codon.

• The different codons use the following table to be translated into their equivalent amino acid.

• The following slide show the code for the DNA and RNA conversion tables.

The genetic code • RNA conversion table DNA conversion table

Adapted from Ref [1] p. 247

What is the amino acid of the DNA sequence transcribed above: TAT

Translation mRNA -> AA• The translation occurs in a component of

the cell called the ribosome.• Translation consists of three phases:• Initiation, elongation and termination

• Stage 1 Initiation: 1. The ribosome attaches to the mRNA

strand and moves to the initiation codon, AUG (ATG on the DNA strand)

2. Then, another version of RNA called, transfer tRNA attaches to the AUG of mRNA

• The tRNA has two essential elements: an anti-codon, e.g. UAC, and an attached amino acid, e.g. methonine.

tRNAAnti-codon

Amino acid: methonine

Adapted from chapter 12 Klug

Initiation of translation

Translation mRNA -> AA• Elongation: • The large subunit of the

ribosome attaches to the strand• The ribosome has three

chambers; going from left to right: – The E site where tRNAs to be

discarded. – The P site: holds the tRNA for

that is attached to the “current” codon.

– The A site: holds the tRNA for the next codon in the mRNA strand: e.g. UUC

Adapted from chapter 12 Klug

Translation mRNA -> AA• Elongation continued: • The amino acid(s) on the P site

join to the amino acid on the A site.

• The ribosome then moves down the mRNA to the next codon ;e.g. GGU.

• In the process 1. The tRNA in the E site is

discarded2. the tRNA in the P site moves to

the E site3. The tRNA and its amino acid

chain in the A site moves to the P site.

Adapted from chapter 12 Klug

Elongation “stage 2”

Translation mRNA -> AA

• Elongation continued: • A new tRNA molecule

with the correct “anti-codon” moves into the empty A chamber.

• A peptide bond is formed between the amino acids in the P and A chamber and step 2 of elongation beings again.

Adapted from chapter 12 Klug

Elongation “stage 3”

Translation mRNA -> AA• Termination : • The ribosome continues to

move down the mRNA strand until it reaches a termination codon; e.g. UGA.

• There is no tRNA corresponding to this codon so the “following” chamber remains empty.

• No peptide bond is formed so when the ribosome moves again it causes the amino acid chain to break of its tRNA and so release the amino acid chain. Adapted from chapter 12 Klug

Animation of the translation process

• Translation Animation

• Translation Animation 2

• Translation animation 3

Exam Question

• Describe, using suitable examples, the steps involved in the “Central Dogma “ of genetics: converting a DNA strand into its corresponding amino acid chain.

References

• [2] http://www.di.uq.edu.au/sparqtransctrans accessed on the 30/09/2011

• [5] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1370565/