Chapter 7 - Control of Gene Expression Flashcards
Post-transcriptional control
Operate after RNA polymerase has bound to the genes promoter and has begun synthesis
Transcription attenuation
Expression of genes I nhibited by premature termination of transcription.
In some cases, the nascent RNA chain adopts a structure that causes it to interact with RNA polymerase in such a way as to abort its transcription.
Example of protein attenuation
HIV
Riboswitches
Short sequences of RNA that change their conformation on binding small molecules, such as metabolites.
Probably ancient form of gene control
Where are Riboswitches usually located?
5’ end of mRNAs and fold while the mRNA is being synthesized - blocking or permitting progress of RNA polymerase
Where are Riboswitches particularly common?
Bacteria - sense key metabolite and adjust gene expression accordingly
Key features of Riboswitches
High specificity and affinity with which each recognizes only the appropriate small molecule.
In many cases, every chemical feature is read by the the RNA completely.
Strong binding affinity
Important functions of riboswitches
Controls transcription elongation and regulate other gene expression
Is the 3’ end of eukaryotic mRNA molecules formed by the termination of RNA synthesis?
No
How does the 3’ end form in eukaryotes?
RNA cleavage reaction catalyzed by additional proteins while the transcript is elongating.
What do B lymphocytes do to activate antibody production?
Increase concentration of CstF protein so that cleavage occurs at suboptimal site and the shorter transcript is produced
Define RNA editing
Alteration of a nucleotide sequence of RNA transcripts once they are synthesized
Deanimation of adenine by inosine (A-to-I editing) and deanimation of cytosine to produce uracil (C-to-U editing).
Effects of RNA editing on coding region
If RNA editing is done in coding sequence, it can change the amino acid of the protein or produce a truncated protein by creating and early stop codon.
Effects of RNA editing outside coding region
Can effect:
- The pattern of pre-mRNA splicing
- The transport of mRNA from nucleus to the cytosol
- The efficiency with which the RNA is translated
- Or the base pairing between microRNAs (miRNAs) and their mRNA targets
Which form of RNA editing is particularly frequent in humans?
A-to-I editing
Approximately in 1000genes
What enzymes perform A-to-I editing?
ADARs (adenosine deaminases acting on RNA).
How do ADARs work?
Identify a ds RNA formed through base pairing between the site to be edited and a complementary sequence located somewhere on the same RNA strand
Structure of the ds RNA specifies whether the RNA should be edited and where it should
A-to-I editing example at transmitter-gate ion channel
Alters a glutamine to an arginine found on the inner walls of the channel
Affects Ca2+ permeability of the channel
Mutant mice that cannot make edit are prone to epileptic seizures
C-to-U binding
Examples
About how much of the RNA actually leaves the nucleus?
1/20
How does HIV overcome the hosts natural block to the nuclear export?
Encode a protein, called Rev, that binds to a specific RNA sequence (called Rev response element (RRE)) located within the viral intron.
rev protein interacts with nuclear export protein (Crm1), which directs the movement of viral RNAs through the nuclear pores into the cytosol despite introns being present.
Where are most localization signals concentrated on the mRNA?
On the 3’ untranslated region (UTR) - region that extends from stop codon to start of poly-A tail.
Normal function to eIF2
Forms a complex with GTP and mediates the binding of the methionyl initiator tRNA to the small ribosomal subunit, which then binds to the 5’ end and begins scanning along the mRNA.
When AUG codon is recognized, the eIF2 protein hydrolyzes the bound GTP to GDP causing conformation change in protein and releasing it from the small ribosomal subunit.
Large subunit then joins small subunit to form ribosome and begin protein synthesis
Function of eIF2B
eIF2 binds tightly to GDP. eIF2B causes GRP release so that a new GTP molecule can bind and eIF2 can be reused.
