Translation Process (Protein Biosynthesis) & The Genetic Code

The Genetic Code

The genetic code is the set of rules by which information encoded in genetic material (DNA or RNA sequences) is translated into proteins (amino acid sequences) by living cells.

mRNA molecules have no affinity for amino acids and, therefore, that the translation of the information in the mRNA nucleotide sequence into the amino acid sequence of a protein requires an intermediate adapter molecule.
This adapter molecule (tRNA) must recognize a specific nucleotide sequence on the one hand as well as a specific amino acid on the other. Twenty amino acids are required for the synthesis of the cellular proteins; thus, there must be at least 20 distinct codons that make up the genetic code. Since there are only 4 different nucleotides in mRNA, each codon must consist of more than a single purine or pyrimidine nucleotide. Codons consisting of two nucleotides each could provide for only 16 (42) specific codons, whereas codons of three nucleotides could provide 64 (43) specific codons.

 The mRNA transcript is a linear sequence of nucleotides carrying genetic information and it is single-stranded.
Every three bases of mRNA (a triplet) specifies an amino acid to be added to a growing polypeptide chain; the relationship between the triplets and the corresponding amino acids is the genetic code.

Each base triplet of mRNA is called a codon. The genetic code is nearly universal for all forms of life.

Features of the Genetic Code

Translation of mRNA (Protein Synthesis)

The entire process of gene expression in eucaryotes includes the following steps: transcription: formation of a primary transcript, the pre-mRNA conversion of the pre-mRNA into the mature mRNA: includes processing, splicing, transport from the nucleus to the cytosol translation: synthesis of the protein on the ribosome. modification posttranslation. Translation is the process by which the nucleotide sequence of mRNA is converveted to the amino acid sequence of a polypeptide. In the first step of the process, all the components needed for translation come together.

messengerRNA (mRNA)

(Kozak Scanning)

Kozak Scanning

Formation of aminoacyl-tRNA
Amino acid activation

aminoacyl-tRNA synthetase

The genetic code is translated by means of two sequential "adaptors". The

first adaptor is the aminoacyltRNA synthetase enzyme, which couples a particular amino acid to its corresponding tRNA; the second adaptor is the tRNA molecule, whose anticodon forms base pairs with the appropriate nucleotide sequence (codon) on the mRNA. An error in either step will cause the wrong amino acid to be incorporated into a protein chain.

The incorporation of an amino acid into a protein. A polypeptide chain grows by the stepwise addition of amino acids to its carboxyl-terminal end. The formation of each peptide bond is energetically favorable because the growing carboxyl terminus has been activated by the covalent attachment of a tRNA molecule.

Decoding an mRNA molecule

Each amino acid added to the growing end of a polypeptide chain is selected by complementary base-pairing between the anticodon on its attached tRNA molecule and the next codon on the mRNA chain.

A comparison of the structures of procaryotic and eucaryotic ribosomes

The elongation phase of protein synthesis on a ribosome

Kinetic proofreading selects for the correct tRNA molecule on the ribosome

The final phase of protein synthesis: The binding of release factor to stop codon terminate translation

The initiation phase of protein synthesis in eucaryotes

Recognition of the codon by the anticodon

Translation initiation pathway in E. coli ribosom

 The flow of genetic information follows the sequence DNA RNA protein. The genetic information in the structural region of a gene is transcribed into an RNA molecule such that the sequence of the latter is complementary to that in the DNA. Ribosomal RNA (rRNA), transfer RNA (tRNA), and messenger RNA (mRNA), are directly involved in protein synthesis; miRNAs regulate mRNA function at the level of translation and/or stability. The information in mRNA is in a tandem array of codons, each of which is 3 nt long. mRNA is read continuously from a start codon (AUG) to a termination codon

The open reading frame, or ORF, of the mRNA is the series of codons, each specifying a certain amino acid, that determines the precise aa sequence of the protein.
Protein synthesis, like DNA and RNA synthesis, follows the 5' to 3' polarity of mRNA and can be divided into three processes: initiation, elongation, and termination.

Mutant proteins arise when single-base substitutions result in codons that specify a different amino acid at a given position, when a stop codon results in a truncated protein, or when base additions or deletions alter the reading frame, so different codons are read. A variety of compounds, including several antibiotics, inhibit protein synthesis by affecting one or more of the steps involved in protein synthesis.

Inhibitors of Protein or RNA Synthesis

Acting Only on Procaryotes*
Tetracycline blocks binding of aminoacyl-tRNA to A-site of ribosome Streptomycin prevents the transition from initiation complex to chain-elongating ribosome and also causes miscoding. Chloramphenicol blocks the peptidyl transferase reaction on ribosomes Erythromycin blocks the translocation reaction on ribosomes Rifamycin blocks initiation of RNA chains by binding to RNA polymerase (prevents RNA synthesis)
Acting Only on Procaryotes and Eucaryotes Puromycin causes the premature release of nascent polypeptide chains by its addition to growing chain end. Actinomycin D binds to DNA and blocks the movement of RNA polymerase (prevents RNA synthesis) Acting Only on Eucaryotes Cycloheximide blocks the translocation reaction on ribosomes. Anisomycin blocks the peptidyl transferase reaction on ribosomes -Amanitin blocks mRNA synthesis by binding preferentially to RNA polymerase II

REGULASI EKSPRESI GEN

Ekspresi gen merupakan keseluruhan proses, di mana

informasi genetik yang disimpan dalam DNA diubah menjadi produk fungsional gen yaitu RNA atau protein.

Tujuan regulasi ekspresi gen adalah agar ekspresinya

terjamin secara akurat baik spatial maupun temporal, sehingga di satu pihak sel dapat beradaptasi terhadap perubahan lingkungan, sedangkan di pihak lain sel dapat tumbuh dan berdiferensiasi secara normal.

Untuk mencapai tujuan tersebut , regulasi ekspresi gen

terjadi dalam berbagai tingkat.

REGULASI EXPRESSI GENE

(1) controlling when and how often a given geneis transcribed (transcriptional control), (2) controlling how the primary RNA transcript is spliced or otherwise processed (RNA processing control), (3) selecting which completed mRNAs in the cell nucleus are exported to the cytoplasm (RNA transport control), (4) selecting which mRNAs in the cytoplasm are translated by ribosomes (translational control), (5) selectively destabilizing certain mRNA molecules in the cytoplasm (mRNA degradation control) (6) selectively activating, inactivating, or compartmentalizing specific protein molecules after they have been made (protein activity control)