1 LC Concepts of Molecular Biology 04.10.2022
The Central Dogma
From the most part the direction of the information goes from the dna to the rna, which then gets
translated into proteins by the ribosome.
The RNA consists of numerous nucleotides that are just attached to each
other, it is formed via the rna polymerase in the direction where we have the
3’ prime carbon of one sugar connected to the 5’ by a phosphodiesterbond.
This bond is a very strong bond, through a reaction that is catalyzed by 2 Mg
(magnesium ions): one come with the polymerase and the other one with the
NTP. every pol elongathes the chain from the 5’ into the 3’ direction.
The Phosphodiester bonds are strong and can endure a long time!
A phosphodiester bond occurs when exactly two of the hydroxyl groups
in phosphoric acid react with hydroxyl groups on other molecules to form two
ester bonds.
In DNA and RNA, the phosphodiester bond is the linkage between the 3'
carbon atom of one sugar molecule and the 5' carbon atom of another,
deoxyribose in DNA and ribose in RNA. Strong covalent bonds form between
the phosphate group and two 5-carbon ring carbohydrates (pentoses) over
two ester bonds
In order for the phosphodiester bond to be formed and the nucleotides
to be joined, the tri-phosphate or di-phosphate forms of the nucleotide
building blocks are broken apart to give off energy required to drive the
enzyme-catalyzed reaction. When a single phosphate or two phosphates
known as pyrophosphates break away and catalyze the reaction, the
phosphodiester bond is formed
Two different systems of transcription:
- PROKARYOTES
Initiation is a single event with consensus DNA elements, small genome (10^6) + 1 core Polymerase
(2x alfa + 2x beta SU) + Sigma factors.
- EUKARYOTES
Consensus DNA elements + enhancers, very large genome (10^9) + 3 polymerases (POL I, II, III), 5
Pols in plants ( Pol IV, V).
, 1 LC Concepts of Molecular Biology 04.10.2022
In eucaryotes:
o POL I
Mostly responsible for transcribing lar ribosomal RNA
o POL II (common: DNA dependent RNA polymerases)
Messenger RNA and differente non-coding RNA
o POL II
Transfer RNAs and small ribosomal RNA
The RNA and the transcription in general is what makes each cell type different, and why it is important
because it allows us to differentiate different cells and their specialization.
>THE BEGINNING OF TRASCRIPTION PROMOTER DNA GAIN ACCESS TO THE DNA
How does the pol know where to transcribe?
The first thing that needs to happen is the recruitment of the Pol and the formation of the so called Pre
Initiation Complex (PIC).
DNA is opened, since it is highly packaged, it is first needed to be unwind in order to do it, there are a
massive amount of TFs transcription factors.
access to the dna can be done by:
- the GC content, yet it happens rarely
- Tata box, where there are regulatory elements
- Transcription factors binding sites close to the promoter
The human genome has 1600 transcription factors that work all together to bind the dna in a very specific
manner, because they recognize specific sequence motives where they can bind the dna.
TRANSCRIPTION FACTORS
TBP: talk about later in this lecture. CTCF we are discussing in a later study
Oct4: interesting TF, since it belongs to the so called Yamanaka factors, together with Sox2, Klf4 and c-myc
can reprogram almost any cell type to pluripotency
Znf410: Lan et al. show that the transcription factor ZNF410 has a single direct target gene, the NuRD
component CHD4, through which it silences the fetal-type b-globin genes in adult erythroid cells. The
exquisite specificity of ZNF410 could be exploited therapeutically for treatment of hemoglobinopathies.
Oct 4: one of Yamanaka factors, he over expressed 4 different genes in fibroblasts and then turned them
back into pluripotent stem cells. Oct 4 is the main driver of this. Oct 4 is expressed a set of cells:
- Early embryonic stem cells
The Central Dogma
From the most part the direction of the information goes from the dna to the rna, which then gets
translated into proteins by the ribosome.
The RNA consists of numerous nucleotides that are just attached to each
other, it is formed via the rna polymerase in the direction where we have the
3’ prime carbon of one sugar connected to the 5’ by a phosphodiesterbond.
This bond is a very strong bond, through a reaction that is catalyzed by 2 Mg
(magnesium ions): one come with the polymerase and the other one with the
NTP. every pol elongathes the chain from the 5’ into the 3’ direction.
The Phosphodiester bonds are strong and can endure a long time!
A phosphodiester bond occurs when exactly two of the hydroxyl groups
in phosphoric acid react with hydroxyl groups on other molecules to form two
ester bonds.
In DNA and RNA, the phosphodiester bond is the linkage between the 3'
carbon atom of one sugar molecule and the 5' carbon atom of another,
deoxyribose in DNA and ribose in RNA. Strong covalent bonds form between
the phosphate group and two 5-carbon ring carbohydrates (pentoses) over
two ester bonds
In order for the phosphodiester bond to be formed and the nucleotides
to be joined, the tri-phosphate or di-phosphate forms of the nucleotide
building blocks are broken apart to give off energy required to drive the
enzyme-catalyzed reaction. When a single phosphate or two phosphates
known as pyrophosphates break away and catalyze the reaction, the
phosphodiester bond is formed
Two different systems of transcription:
- PROKARYOTES
Initiation is a single event with consensus DNA elements, small genome (10^6) + 1 core Polymerase
(2x alfa + 2x beta SU) + Sigma factors.
- EUKARYOTES
Consensus DNA elements + enhancers, very large genome (10^9) + 3 polymerases (POL I, II, III), 5
Pols in plants ( Pol IV, V).
, 1 LC Concepts of Molecular Biology 04.10.2022
In eucaryotes:
o POL I
Mostly responsible for transcribing lar ribosomal RNA
o POL II (common: DNA dependent RNA polymerases)
Messenger RNA and differente non-coding RNA
o POL II
Transfer RNAs and small ribosomal RNA
The RNA and the transcription in general is what makes each cell type different, and why it is important
because it allows us to differentiate different cells and their specialization.
>THE BEGINNING OF TRASCRIPTION PROMOTER DNA GAIN ACCESS TO THE DNA
How does the pol know where to transcribe?
The first thing that needs to happen is the recruitment of the Pol and the formation of the so called Pre
Initiation Complex (PIC).
DNA is opened, since it is highly packaged, it is first needed to be unwind in order to do it, there are a
massive amount of TFs transcription factors.
access to the dna can be done by:
- the GC content, yet it happens rarely
- Tata box, where there are regulatory elements
- Transcription factors binding sites close to the promoter
The human genome has 1600 transcription factors that work all together to bind the dna in a very specific
manner, because they recognize specific sequence motives where they can bind the dna.
TRANSCRIPTION FACTORS
TBP: talk about later in this lecture. CTCF we are discussing in a later study
Oct4: interesting TF, since it belongs to the so called Yamanaka factors, together with Sox2, Klf4 and c-myc
can reprogram almost any cell type to pluripotency
Znf410: Lan et al. show that the transcription factor ZNF410 has a single direct target gene, the NuRD
component CHD4, through which it silences the fetal-type b-globin genes in adult erythroid cells. The
exquisite specificity of ZNF410 could be exploited therapeutically for treatment of hemoglobinopathies.
Oct 4: one of Yamanaka factors, he over expressed 4 different genes in fibroblasts and then turned them
back into pluripotent stem cells. Oct 4 is the main driver of this. Oct 4 is expressed a set of cells:
- Early embryonic stem cells
