Translation

MCB 2400: Human Genetics

Chapter 10: Translation

Overview

  • Translation is the process by which proteins are synthesized from mRNA.

  • Involves various types of RNA: mRNA (messenger RNA), tRNA (transfer RNA), and ribosomal RNA (rRNA).

  • Newly synthesized proteins are formed by linking amino acids through peptide bonds.

  • Major components involved:

    • tRNA: Transfers the appropriate amino acids to the ribosome.

    • mRNA: Provides the sequence information for protein synthesis.

    • Ribosomes: Catalyst for protein synthesis, made up of rRNA and proteins.

Key Terms and Components

  • tRNA: Transfer RNA that carries amino acids to the ribosome.

  • mRNA: Mature messenger RNA that directs protein synthesis.

  • Amino acids: Building blocks of proteins; there are 20 different amino acids.

  • Large subunit and small subunit of ribosomes: Two distinct parts that come together during translation.

  • A site (Aminoacyl site): Binds incoming tRNA carrying amino acids.

  • P site (Peptidyl site): Holds the tRNA linked to the growing polypeptide chain.

Structure of Messenger RNA (mRNA)

  • Protein Coding Region: Series of nucleotides that specify which amino acids to add during translation.

  • 5' Untranslated Region (5’ UTR): Essential for ribosome binding and intron splicing.

  • 3' Untranslated Region (3’ UTR): Plays a regulatory role in mRNA stability and translation efficiency.

  • 5’ Methyl Cap: Added during mRNA processing which protects the mRNA from degradation.

  • AAAA Tail: Series of adenine nucleotides added to the 3' end of mRNA, stabilizing it and aiding in translation.

Protein Structure and Function

  • Proteins: Essential building blocks of all living organisms.

  • Examples:

    • Luciferase: An enzyme that produces bioluminescence.

    • Fibroin: A structural protein found in spider silk.

  • Key components of proteins:

    • Z disk, M line, and Actin contribute to muscle structure and function.

    • Titin provides elasticity and stabilizes myosin filaments.

    • Myosin: Another essential protein involved in muscle contraction.

Amino Acids - The Building Blocks of Proteins

  • Classification of amino acids:

    1. Nonpolar: Glycine (Gly, G), Alanine (Ala, A), Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I), Methionine (Met, M)

    2. Polar: Serine (Ser, S), Threonine (Thr, T), Cysteine (Cys, C), Proline (Pro, P), Asparagine (Asn, N), Glutamine (Gln, Q)

    3. Aromatic: Phenylalanine (Phe, F), Tyrosine (Try, Y), Tryptophan (Trp, W)

    4. Positively Charged: Lysine (Lys, K), Arginine (Arg, R), Histidine (His, H)

    5. Negatively Charged: Aspartate (Asp, D), Glutamate (Glu, E)

  • Each amino acid features:

    • Amino Group: -NH_2

    • Carboxyl Group: -COOH

    • Radical Group (R group): Varies between different amino acids, influencing their properties.

    • Peptide bonds connect amino acids in chains to form polypeptides.

Levels of Protein Organization

  • Primary Structure: Sequence of amino acids in a polypeptide chain.

  • Secondary Structure: Local folding into shapes like alpha-helices and beta-pleated sheets.

  • Tertiary Structure: Overall 3D shape of a protein, dependent on interactions between R groups.

  • Quaternary Structure: Complex formation between multiple polypeptide chains.

  • Molecular Chaperones: Assist in proper folding of newly synthesized proteins.

  • Post-translational Modifications: Chemical modifications after protein synthesis that can alter function and localization.

Translation Process

  1. Initiation:

    • mRNA binds to the small ribosomal subunit.

    • Ribosome scans the mRNA for a START codon (AUG) surrounded by a Kozak sequence (5’ – ACCAUGG – 3’).

    • tRNAfMet (initiator tRNA) binds at the P site.

    • The large ribosomal subunit binds to complete the ribosome assembly.

  2. Elongation:

    • Charged tRNAs enter the A site, and amino acids are linked via peptide bonds.

    • The ribosome translocates to the next codon on the mRNA.

    • Process repeats until a stop codon is reached.

  3. Termination:

    • No tRNA corresponds to stop codons (UAA, UAG, UGA).

    • Release factors (RFs) bind to the A site, prompting the release of the polypeptide chain.

    • Disassembly of the ribosomal complex occurs, and mRNA, tRNAs, and RFs are released.

The Genetic Code

  • Composed of triplet codons: Each codon corresponds to one amino acid.

  • Degeneracy: More than one codon can encode for the same amino acid.

  • There are 64 possible codons for 20 amino acids (using 4 bases A, U, G, C).

  • Stop Codons: UAA, UAG, and UGA signal the end of translation.

  • Wobble Hypothesis: Relaxation of base-pairing rules at the third position of the codon.

  • The genetic code is non-overlapping and can be read in three different frames, with the open reading frame (ORF) defined from the start codon to a stop codon.

Distinct Sites of the Ribosome

  • A site: Where tRNA enters with its amino acid.

  • P site: Holds the tRNA carrying the growing polypeptide chain.

  • E site: Exit site where empty tRNA leaves the ribosome.

Further Exploration

  • The intricate processes of amino acid linkage, translation initiation, elongation, and termination highlight the complexity of genetic expression and protein synthesis within cells.