Gene expression control Flashcards
How can a cell control the proteins it makes?
- Controlling when and how often a given gene is transcribed (transcriptional control)
- Controlling the splicing and processing of RNA transcripts (RNA processing control)
- Selecting which completed mRNAs are exported from the nucleus to the cytosol and determining where in the cytosol they are localized (RNA transport and localization control)
- Selecting which mRNAs in the cytoplasm are translated by ribosomes (translational control)
- Selectively destabilizing certain mRNA molecules in the cytoplasm (mRNA degradation control)
- Selectively activating, inactivating, degrading, or locating specific protein molecules after they have been made (protein activity control)
What type of control controls when and how often a given gene is transcribed?
Transcriptional control
What type of control controls the splicing and processing of RNA transcripts?
RNA processing control
What type of control selects which completed mRNAs are exported from the nucleus to the cytosol and determines where in the cytosol they are localized ?
RNA transport and localization control
What type of control selects which mRNAs in the cytoplasm are translated by ribosomes?
Translational control
What type of control selectively destabilises certain mRNA molecules in the cytoplasm?
mRNA degredation control
What type of control selectively activates, inactivates, degrades, or locates specific protein molecules after they have been made?
Protein activity control
What are gene regulatory proteins?
Proteins that turn specific sets of genes on or off
The ______** of the double helix is studded with DNA sequence _________ that ____ _________ proteins can recognize without having to ____ **the double helix.
The **outside **of the double helix is studded with DNA sequence **information **that **gene regulatory **proteins can recognize without having to **open **the double helix.
The edge of each base pair is exposed at the ______ of the _______ _____, presenting a distinctive pattern of hydrogen bond _______, hydrogen bond _________, and _________ patches for proteins to recognize in both the major and minor ______.
The edge of each base pair is exposed at the surface of the double helix, presenting a distinctive pattern of hydrogen bond donors, hydrogen bond acceptors, and hydrophobic patches for proteins to recognize in both the major and minor groove.
Which groove in DNA is recognised by gene regulatory proteins?
The major groove
Define DNA binding domain
An independently folded protein domain that contains at least one motif that recognizes double- or single-stranded DNA.
What are the types of DNA binding domain motifs?
- helix-turn-helix
- helix-loop-helix
- zinc finger
- leucine zipper
Describe the DNA binding protein motif helix-turn-helix
- It is constructed from two alpha helices connected by a short extended chain of amino acids, which constitutes the “turn”
- The two helices are held at a fixed angle
- The more C-terminal helix is called the recognition helix because it fits into the major groove of DNA
What are homeotic selector genes?
Genes that play an essential part in orchestrating fly development
Define homeodomain
The class of proteins called the homeotic selector genes
Describe the DNA binding protein motif zinc fingers
- It includes one or more zinc atoms as structural components
Describe the DNA binding motif leucine zipper
- Two alpha helices are joined together to form a short coiled-coil
- The helices are held together by interactions between hydrophobic amino acid side chains (often on leucines) that extend from one side of each helix
Heterodimerization is an example of ___________ ________, in which combinations of different proteins, rather than individual proteins, control a cell process
Heterodimerization is an example of combinatorial control, in which combinations of different proteins, rather than individual proteins, control a cell process
Describe the DNA binding motif helix-loop-helix (HLH)
- Consists of a short alpha helix connected by a loop to a second, longer alpha helix
- this two-helix structure binds both to DNA and to the HLH motif of a second HLH protein
- The second HLH protein can be the same (creating a homodimer) or different (creating a heterodimer)
What is epigenetic regulation?
Regulation by epigenetic changes that can modify the activation of certain genes, but not the sequence of DNA
What are some examples of epigenetic mechanisms?
DNA methylation:
- at CpG dinucleotides
- of the gene promoter
What are the two ways histones can be modfied to make changes in transcription?
Histone acetylation activates transcription, and histone methylation silences transcription
What is the activation domain?
The domain that activates transcription
What is gene expression that is temporarily altered?
**Induced **expression
The extent of the differences in ____ _________ between different cell types may be roughly gauged by comparing the _______ composition of cells in the liver, heart, brain and so on using the technique of ___-__________ gel electrophoresis.
The extent of the differences in gene expression between different cell types may be roughly gauged by comparing the **protein **composition of cells in the liver, heart, brain and so on using the technique of two-dimensional gel electrophoresis.
What is a** repressor**?
A protein, when in its active form, switches genes off
What are **activator **proteins?
Proteins that activate genes
What are some examples of “housekeeping” genes and proteins?
- Structural proteins in chromosomes
- RNA polymerases
- DNA repair enzymes
- Ribosomal proteins
- Metabolic enzymes
Some genes are needed in only ______ tissues, therefore a more specific technique is needed to detect them called ____ ____________.
Some genes are needed in only certain tissues, therefore a more specific technique is needed to detect them called mass spectrometry.
Some genes will only be expressed at certain stages of a cell’s life. What are some of these stages?
- developmental stage
- differentiation stage
- cell cycle stage
- inducible expression
What is the gene control region?
The whole expanse of DNA involved in regulating and initiating transcription of a gene.
The term **gene control region is often used to describe the whole expanse of DNA involved _________ and ________ transcription of a ____, including the ________, where general transcription factors and the polymerase assemble, and all of the ________ __________ **to which gene regulatory proteins bind to control the rate of the assembly process at the _______.
The term **gene control region **is often used to describe the whole expanse of DNA involved regulating and initiating transcription of a gene, including the promoter, where general transcription factors and the polymerase assemble, and all of the **regulatory sequences **to which gene regulatory proteins bind to control the rate of the assembly process at the promoter.
How can gene expression be induced?
- small molecules bind to specific DNA sequences in promoters
- this activates transcription factors
- transcription initiated
What is an example of induced gene expression in humans?
The Glucocorticoid receptor protein
In response to ___________, liver cells increase the expression of many different genes, one of which encodes the enzyme _______ _____________. These genes are all regulated by the binding of the _____________ ________-________complex to a regulatory sequence in the DNA of each gene. When the hormone is no longer present, the ___________ of the genes drop to its normal level.
In response to glucocorticoids, liver cells increase the expression of many different genes, one of which encodes the enzyme tyrosine aminotransferase. These genes are all regulated by the binding of the glucocorticoid hormone-receptor complex to a regulatory sequence in the DNA of each gene. When the hormone is no longer present, the expression of the genes drop to its normal level.
Some molecules are too big to pass through the plasma membrane, how can they affect gene expression?
Through surface receptors which activate messengers that can activate transcription factors
What is signal transduction?
The conversion of a signal outside the cell to a functional change inside the cell
What are some of the post-transcriptional controls?
- alternative splicing
- alternative polyadenylation
- tissue specific RNA editing
- regulation of translation
How can translation be regulated?
- cis-acting regulatory sequences present in untranslated regions (UTRs) of mRNA:
- targeted by trans-acting **RNA binding proteins **to promote or regulate longetivity of mRNA
- targeted by **micro RNA (miRNA) **to inhibit translation or degrade RNA
What’s an example of alternative polyadenylation?
The calcitonin gene
What is the “untranslated region (UTR)”?
The three prime untranslated region (3’-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon
What’s an example of translation regulation in response to external stimuli?
iron / IRE-BP / IRE in ferritin and TfR mRNA
How can micro RNAs (miRNAs) control gene expression?
They can inhibit translation and cleave mRNAs
Once made, miRNAs base-pair with specific _____ and regulate their stability and their translation. The miRNA _________ are synthesised by RNA polymerase _ and are capped and _____________. They are then processed and assembled with _______ to form a RISC (___-________ _________ _______). The RISC then seeks out complementary mRNA sequences and targets the __ end of the UTRs.
Once made, miRNAs base-pair with specific mRNAs and regulate their stability and their translation. The miRNA **precursors **are synthesised by RNA polymerase **II **and are capped and **polyadenylated. They are then processed and assembled with proteins **to form a RISC (RNA-induced silencing complex). The RISC then seeks out complementary mRNA sequences and targets the 3’ end of the UTRs.
What protein facilitates the cleavage of mRNA by miRNA?
Argonaute
How is a protein’s final function controlled?
- cleavage (e.g. proinsulin → insulin)
- presence of inhibitors of protein activity
- other functional modifications (glycolysation, phosphorylation)
- control of protein degredation
