1. DNA TRANSCRIPTION
Making mRNA

2. Gene Expression
The human genome contains about 20,325 protein-encoding genes(exomes), however, this represents only a small part of the genome, about 1.5%
Much of the human genome controls protein synthesis; including time, speed, and location
Proteins are the molecules of structure and function. They have many diverse functions including:

3. From DNA to Protein Production of protein from instructions on the DNA
Gene expression requires several steps
- Transcription = Production of mRNA in the nucleus
- Translation = Production of protein using mRNA, tRNA, and ribosomes(rRNA) in cytoplasm
- Folding of the protein into the active 3-D form, usually within the Golgi Complex
Transcription and translation occur continuously, except during M phase
Polypeptide chain
Golgi Complex

4. Transcription the Basics
To ‘transcribe’ means to ‘write across’
RNA is the bridge between DNA and protein
RNA is synthesized from one strand of the DNA double helix: the template strand
The complementary strand is called the coding strand of DNA
Requires the enzyme RNA polymerase
Chaos would ensue if all genes were being transcribed and translated at the same time…to manage the synthesis of proteins special molecules called transcription factors are activated in response to signals(hormones) and bind to the sites of specific genes and initiate transcription

5. Transcription Factors
Complex organisms transcription factors control gene expression and link the genome to environment
- about 2,000 in humans
Often work together to provide great specificity in controlling gene expression. For example: lack of oxygen, such as from choking or smoking, sends signals that activate transcription factors to turn on dozens of genes that enable the cell to handle the stress of low-oxygen conditions
Mutations in transcription factors may cause a wide range of effects, because the factors control many genes.
Transcription factors are controlled by each other

6. Transcription Process
Transcription is described in three steps:
- Initiation
- Elongation
- Termination

7. Step 1: Initiation How do TFs and RNA polymerase ‘know’ where to begin transcribing a certain gene?
In transcription initiation, a cascade of transcription factors bind to the promoter region of a gene
These open a pocket allowing the RNA polymerase to bind just in front of the start of the gene sequence
Binding proteins that initiate transcription recognize specific sequences in the promotor region of a gene
A binding protein recognizes the TATA region and binds to the DNA, allowing other TFs to bond
The bound TF form a pocket that allows RNA polymerase to bind and begin making RNA

8. Step 2: Elongation
Enzymes unwind the DNA helix at the gene site, and free RNA nucleotides bond with exposed complimentary bases on the DNA template strand
During elongation, RNA polymerase reads the nucleotides on the template strand from 3’ to 5’ and creates an RNA molecule in a 5’ to 3’ direction
Transcription rate in humans is about 20 bases per second
Elongation continues until the RNA polymerase reaches the end of the gene sequence marked by the terminator sequence

9. Step 3: Termination
A terminator sequence in the DNA indicates where the gene’s RNA-encoding region ends
When this spot is reached transcription termination is initiated and the RNA polymerase detaches
A short complementary GC-rich sequence, followed by several U’s will form a loop and "brake" polymerase causing it to detach
Transcription

10. Simultaneous Transcription
Several mRNAs may be transcribed from the same template DNA strand at a time; this is because mRNA is short lived, with about half of it degraded every 10 minutes, a cell must constantly transcribe mRNA to keep up with supplies of essential proteins

11. RNA Processing
In eukaryotes, mRNA transcripts are modified before they leave the nucleus
Several steps process pre-mRNA into mature mRNA
1) A methylated cap is added to the 5’ end
- Recognition site for protein synthesis
2) A poly-A tail(approx 200 Adenines) is added to the 3’ end
- Stabilizes the mRNA
3) Splicing occurs
- Introns (“intervening sequences”) are removed
- Exons (“expressed sequences”) are spliced together
- Note that introns may outnumber and outsize exons
Finally, the mature mRNA is sent out of the nucleus

12. Introns? Why? Introns are common and large in human genes
Range in size from 65-10,000 or more bases
The coding exon of the average genes is 1,340 bases, where as the average total size of a gene is 27,000 bases
The dystrophin gene=2,500,000 bases, but it’s corresponding mRNA is only 14,000 bases. The gene contains 80 introns
Before discovery in the 70’s geneticists thought gene sequences were like sentences where all of the information has meaning
Introns became known as “junk DNA”; not quite accurate
Some code for RNAs that control gene expression
Some may be atavisms remnants of ancient genes that have lost their original function
Remnants of DNA or viruses that once integrated into a strand onto a chromosome
Some are actually exons on the complimentary strand of DNA