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2. gene to protein
1. Central Dogma: Gene to
Protein
Themba Hospital FCOG(SA) Part 1 Tutorials
By Dr N.E Manana
2. Introduction
• Francis Crick proposed the central dogma of molecular biology.
Three eukaryotic cellular RNA polymerases :
• Polymerase I transcribes ribosomal RNAs
• Polymerase II transcribes all messenger RNAs (mRNAs) plus a number of
small RNA molecules;
• And polymerase III transcribes transfer RNAs (tRNAs)
• Each gene contains a specific sequence of nucleotides. This sequence of
nucleotides specifies which sequence of amino acids should be joined
together to form the protein
3.
4. Transcription
• Transcription is the process that makes messenger RNA (mRNA)
• mRNA is a single-stranded polymer of nucleotides
• The shape and chemical makeup of the nucleotides ensure that only
one type of RNA nucleotide can pair with each DNA nucleotide
• Thymine is replaced by uracil in RNA, so A in DNA pairs with uracil in
mRNA
5.
6. Transcription
• This geographic segregation, in which mRNAs are created and used in,
has allowed structurally complex genes whose RNA products are
spliced before use
• Most protein-coding genes contain protein-coding regions called
exons separated by noncoding intron regions
• The initial RNA copy of these genes must be processed to remove the
introns before the mRNA is exported from the nucleus
7. Translation
• Each set of three nucleotides in an mRNA molecule codes for one amino
acid
• This explains why each set of three nucleotides in the mRNA is called a
codon
• The sequence of codons in the mRNA determines the sequence of amino
acids in the protein
• Each tiny ribosome provides a workbench with the structure and enzyme
needed for translation
• A special type of RNA, transfer RNA (tRNA), is required to ensure that the
correct amino acid is brought in to match each codon in the mRNA
8.
9. Gene Expression
• Each organism, whether it has 600 genes (Mycoplasma), 6000 genes
(budding yeast), or 25,000 genes (humans), depends on reliable
mechanisms to regulate the expression of these genes
• Cells send each other signals that control gene expression
• Control is exerted at multiple steps, including production of
messenger RNA (mRNA), translation, and protein turnover.
• Proteins called transcription factors (TFs) turn genes on or off
: that DNA is transcribed into RNA and that this RNA is then translated into protein
transcription requires an enzyme, RNA polymerase, which separates the two strands of DNA and adds RNA nucleotides, one at a time, to form the mRNA molecule
The initial RNA products of transcription of most eukaryotic genes require extensive modifications by RNA processing before they are ready to function
Cells also contain enzymes that fragment doublestranded RNAs into small pieces, used by other proteins to direct the silencing of the genes that encoded them. This process of RNA interference (RNAi) is critical for defense against RNA viruses and in chromatin regulation
Although some proteins fold spontaneously into their mature form following release from a ribosome, many proteins require a helping hand to reach their properly folded state.
In eukaryotes, TFs are numerous, representing approximately 6% of human genes. They are also quite diverse, binding to a wide range of DNA regulatory sites.
Three types of eukaryotic DNA-dependent RNA polymerases respond to these regulatory proteins and transcribe DNA sequence into RNA. Regulation of TFs is achieved by variations in a limited number of mechanisms that control their synthesis, transport from the cytoplasm into the nucleus, activity through posttranslational modifications or binding to small molecular ligands.
by binding to DNA regulatory sequences associated with sequences encoding the protein or RNA product of the gene
Synthesis of RNA by RNA polymerases is a cyclic process that can be broken down into three sets of events: initiation, elongation, and termination
In the first step of the initiation process, RNA polymerase binds to the chromosome near the beginning of the gene, forming a preinitiation complex at a sequence termed a promoter.
Next, a conformational change in the polymerase–promoter complex separates the DNA strands. This open complex allows RNA polymerase access to singlestranded nucleotide bases that serve as the template to start the transcript.
Eukaryotic cells have a bewildering array of RNA species that perform many different, key functions in gene expression. The mature forms of all these RNAs are generated by RNA processing reactions, so the RNA processing machinery is of considerable importance. Probably for this reason, RNA-processing enzymes and cofactors are generally highly conserved during eukaryotic evolution. For many RNA species, transcription and maturation are closely coupled and can be thought of as an integrated system. Finally, it is notable that many RNA species and functionally important modifications have only recently beendiscovered, so there is every reason to think that additional classes of RNA remain to be identified.