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Transcription cannot occur and regulate gene expression if...

...we cannot also regulate the downstream products of transcription.


What are the post-transcriptional steps that control gene expression that occur in the nucleus?

1. Attenuation/riboswitches
2. RNA processing control, alternative splicing, capping, cleavage/polyadenylation
3. RNA editing


What are the post-transcriptional steps that control gene expression that occur in the cytoplasm?

1. Translation control, localization control, translation initiation
2. mRNA stability
3. Protein control, turnover, modification, and inhibition


Alternative splicing can lead to over ___ proteins.



What are the four common types of alternative splicing?

1. Exon skipping
2. Alternative 3' splice site selection
3. Alternative 5' splice site selection
4. Intron retention


What are the three uncommon types of alternative splicing?

1. Mutually exclusive exons
2. Alternative promoters
3. Alternative polyadenylation


Describe the way alternative splicing affects the fibronectin gene.

Fibroblast fibronectin and hepatocyte fibronectin are encoded by the same gene. Fibroblasts synthesize mRNA that contains the exons EIIIA and EIIIB, which encode protein regions responsible for binding the cell membrane. Hepatocytes splice out these exons.


What is the different between fibroblast fibronectin and hepatocyte fibronectin?

Fibroblast fibronectin is insoluble and is a part of the extracellular matrix that binds to the cell membrane; it is involved in cell adhesion. Hepatocyte fibronectin is soluble and circulates in serum; it is important in clot formation.


The Drosophila DSCAM gene can produce ___ different splicing patterns.



Variants of the DSCAM gene contribute to what functions in Drosophila?

1. Plasticity of the immune system and formation of complex neural circuits
2. Mediate phagocytosis of bacterial pathogens


How do regulatory proteins aid in the selection of splice sites?

Regulatory proteins either promote or block the use of specific splice sites by binding to regulatory sequences in pre-mRNA; called splice site enhancers and silencers, respectively.


Describe negative control of splice site selection.

A strong splice signal will likely be used no matter what, unless it is inhibited. A repressor interacts with a silencer sequence and discourages splicing. This is NOT a physical blockade.


Describe positive control of splice site selection.

A weak splice signal will likely be ignored unless it is enhanced. An activator interacts with an enhancer sequence and encourages splicing.


SR proteins recruit ___ components to 5' and 3' splice sites. How does this function in genes that cannot do alternate splicing?

Spliceosome; these proteins ensure correct splicing in instances without possible alternative splicing


SR proteins are rich in what two amino acids?

Ser and Arg


What is the difference between constitutive splicing and alternative splicing?

In alternative splicing, the levels of the activator and repressor proteins vary between tissues.


The choice of ___ and ___ sites in a pre-mRNA can affect the protein product of a gene.

Cleavage; polyA sites


Describe regulation of 3' end processing of immunoglobulin mRNAs in B cells.

In a resting B cell, a long RNA transcript is produced and splicing of the intron occurs; the cell uses the strong splice site. The membrane-bound antibodies are produced. In an activated B cell, the weak site is used, the transcript is cleaved, and polyadenylated upstream of the splice site. This leads to the hydrophilic portion of the secreted antibody.


___ CstF leads to a resting B cell. ___ CstF leads to an activated B cell. CstF interacts with the ___ site.

Decreasing; increasing; poly-A.


In eukaryotic cells, the ___ of translation initiation is more common than the regulation of individual mRNAs.

Global regulation


What leads to inhibition of protein synthesis in regulation of translation?

Phosphorylation of eIF-2


Describe the eIF2 cycle.

1. GDP-bound eIF2 is inactive.
2. Inactive eIF2 binds eIF2B
3. GDP is removed from eIF2*eIF2B and GTP is added.
4. GTP-bound eIF2 is active.

When inactive GDP-bound eIF2 is phosphorylated by a kinase, it binds and sequesters eIF2B.


What is the cap-binding protein?



Describe the regulation of eIF4E.

eIF4E is activated by growth factors resulting in phosphorylation of eIF4E-BP (binding protein), an eIF4E inhibitor. This phosphorylation causes eIF4E-BP to leave; eIF4E is then able to bind eIF-4G, which is required to recruit the small ribosomal subunit. Dephosphorylation of eIF4E-BP (triggered by serum deprivation, viral infection, heat shock, and M phase) occurs. eIF4E-BP binds to eIF4E, preventing its binding with eIF4G and inhibiting synthesis.


Some mRNAs contain ___ with features that inhibit translation.

5' untranslated regions (5'-UTRs)


What is an inefficient mRNA?

Inefficient mRNA contains long 5'-UTR with extensive secondary structure of AUG codons upstream of the translation start site.


What happens to inefficient mRNA when eIF4E levels are low? What happens to efficient mRNA when eIF4E levels are low?

It is poorly translated; it is translated well.


Inefficient mRNA typically encodes proteins involved in cell growth and cell cycle regulation. Why?

This helps protect against cancer, since these genes can be considered proto-oncogenes.


mRNA containing an IRES can be...

...translated independent of a N7-methylguanine cap. IRES allows the 40S subunit to bypass the cap when forming a functional translation initiation complex with the corresponding mRNA. Thus, inhibition of eIF4 by eIF4-BP does not stop translation of mRNAs containing IRES. In fact, inhibition of eIF4 by eIF4-BP likely activates translation of mRNAs containing IRES.


Give an example of the use of IRES.

Activation of apoptosis; initiated by caspases, which target eIF4G. This turns off synthesis of many cellular proteins while activating synthesis of proteins needed for cell death. These mRNA likely contain IRES.