Gene expression Flashcards
Selective gene expression allows cells to
efficient, synthesizing only what is needed for each cell type
Multicellular eukaryotes consists of and is distinguished based on
a mixture of specialized or differentiated cell types
based on difference in appearance and protein products
Cell differentiation
Differentiated cells are produced from groups of immature, non-specialized cells or undifferentiated cells
What are the five levels of gene expression
- Genome
- Transcription
- RNA processing and export
- Translation, and
- Posttranslational events
Posttranscriptional control
What does Gene amplification
do?
selective replication of specific genes rRNA genes Xenopus laevis (5.8S, 18S, 28S rRNAs) 500 genes in haploid genome 4000-fold replication during oogenesis 2 million copies in mature oocyte
mammalian RBCs discard nuclei after enough hemoglobin mRNA is made
Gene deletion
DNA rearrangement is when
Movement of DNA segments from one location to another within the genome
DNA Methylation is associated with
Inactive Regions of the Genome
Addition of methyl groups to selected cytosine bases does what
silencing of gene expression
-(methylated cytosine tend to cluster near the 5’ ends of the genes – cause methylation of promoters)
Methylation patterns are ___ and can cause
inherited
causes epigenetic changes
some degree of chromatin decondensation (unfolding) is necessary for
the expression of eukaryotic genes
- to give transcription factors and RNA polymerase access to DNA
DNA is packaged by ____ that bid to the DNA
Histone proteins
Tagging of histone molecules by acetyl, methyl and phosphate groups has a ___ which creates ___
protruding tail that can be tagged which can create a histone code
a group of non-histone proteins associated with isolated chromatin
HMG
What has large contents of HMG
Transcriptionally active chromatin
General transcription factors – essential for transcription of all the genes transcribed by a
given type of RNA polymerase
General transcription factors assemble with RNA polymerase II at
the core promoter, a region immediate to start point and starts transcription at a low level
Regulatory transcription factors
increase (or decrease) transcription initiation
Proximal Control Elements are located
Located upstream (100-200 bp) & close to core promoter
What is the difference between activators and repressors
Enhancers stimulate gene expression
Silencers inhibit gene expression
What are the two principles govern the interaction between enhancers and the genes they regulate
- Looping - brings enhancer closer to core promoter
- Coactivator proteins - mediate the interaction between activators and RNA polymerase complex bound to core promoter
Modify chromatin/nucleosome structure
Coactivator proteins
– SWI/SNF family of coactivators
What allow non-adjacent genes to be regulated in a coordinated fashion
- turn transcription on or off
- environmental or developmental signals
DNA response elements
What is post transcriptional regulation
After transcription, the flow of genetic information involves a complex series of posttranscriptional events, any or all of which can turn out to be regulatory points
post transcriptional regulation can control by:
- RNA processing and nuclear export,
- initiation factors and translational repressors,
- regulation of mRNA degradation,
- RNA interference and
- modifications of protein structure, function and degradation
What does RNA processing do?
Addition of 5’ cap and a 3’ tail
- Chemical modifications such as methylation - Alternative splicing – splicing together of exons removing introns, important control as it makes a variety of mRNAs from the same pre-mRNA;
After processing, export of mRNA through nuclear pores to the cytoplasm
RNAs with defects in capping or splicing are not readily exported from the nucleus
Nuclear export
Transport of mRNA through nuclear pores does not take place until their export is
trigger by a stimulus signal
The amino acid sequence of the Rev protein includes a _____ to guide the viral RNA out through the nuclear pores into the cytoplasm
nuclear export signal
Once mRNA is in the cytoplasm, these are available to regulate the translation of mRNA to polypeptide
translational control mechanisms
Translational control mechanisms work by
- altering ribosomes or protein synthesis factors or
- regulating the activity or stability of mRNA
Synthesis of globin polypeptide depends on the availability of ‘heme’ which
the iron-containing prosthetic group that attaches to globin to form the final product, hemoglobin.
Synthesis of ferritin, an iron-storage protein, is selectively
stimulated in the presence of iron.
The half-life of eukaryotic mRNAs varies widely ranging from 30 minutes or less for some growth factors, and over 10 hours for the mRNA encoding β-globulin
Regulation of mRNA degradation
The length of poly(A) is one factor that plays a role in
controlling mRNA stability
are mRNA with short poly(A) tails more or less stable
less stable
RNA interference or RNAi – based on ability of small RNA to
trigger mRNA degradation, or
inhibit mRNA translation, or
inhibit transcription of the gene coding for a particular mRNA
RNA interference utilizes small RNAs to
to silence the expression of genes
RNA interference by dsRNA:
A cytoplasmic nuclease known as ___ cuts dsRNA into 21-22bp fragments (siRNA)
Dicer
RNA interference by dsRNA:
siRNA binds RISC proteins and one strand is
degraded
siRISC (remaining strand + RISC) binds to mRNA via
complementary base pairing
MicroRNAs (miRNAs) are a class of
single-stranded RNAs about 21-22 nt in length that are produced by genes found in almost all eukaryotic cells
miRNAs bind to and regulate
regulate the expression of mRNAs
Genes coding for miRNAs accounts for up to 5% of eukaryotic genes
What plays an important role in embryonic development
Translational silencing by microRNAs
What are Posttranslational modifications of protein structure, function
Once polypeptide chain is formed - still many ways of regulating the activity of polypeptide chain
These are posttranslational control mechanisms that are available for modifying protein structure and function
Protein degradation are mechanisms that control the amount of any given protein present in a cell is influenced by its
rate of degradation and rate of production
The half-lives of cellular proteins range from a
few minutes to several weeks
dependent protein degradation
Ubiquitin
What is Ubiquitin
a small protein chain of 76 amino acids, and is joined to target proteins by a process that involves three components
What are the three components of Ubiquitin
E1: Ubiquitin-activating enzyme
E2: Ubiquitin-conjugating enzyme
E3: substrate recognition protein
Ubiquitin is first activated by attaching it to __ in an ATP-dependent reaction
E1
Activated ubiquitin is transferred to E2 and subsequently linked to __ residue in the target protein, in a reaction facilitated by E3
Lys
ubiquitin chains serve as targeting signals that are recognized by protein degrading structures, called
‘Proteasomes’
