August 14 2019 Post-transcriptional Controls Prote Flashcards
How are PTB expression levels regulated?
PTB regulates its own expression levels by forcing exclusion of exon 11 from its own mRNA; PTB activates exon 11 skipping in its own transcript via binding to phylogenetically conserved CU-rich sequences surrounding exon 11
What is the role of PTB in smooth muscle cell alpha-tropomyosin pre-mRNA splicing?
In smooth muscle cells, PTB represses inclusion of exon 3 in the mature mRNA
What is the role of RBM4 on alpha-tropomyosin pre-mRNA splicing, and in which muscle type is it highly expressed?
RBM4 is an enhancer of splicing, and promotes inclusion of exon 9a; it is highly expressed in skeletal muscle
What does NMD stand for and what is its main function?
NMD stands for nonsense-mediated decay. Its main function is to reduce errors in gene expression by eliminating mRNA transcripts that contain premature stop codons.
Describe the antiviral response by interferon.
Virus infection activates many transcription factors, including NF-kB
Type I interferons (alpha/beta) are secreted by virally-infected cells
Bind to IFN receptors on adjacent cells
Stimulates “anti-viral” state in those cells
IFN-receptor interaction activates STATs->genes stimulated, including PKR->PKR phosphorylates eIF2alpha, which can no longer deliver tRNA to ribosome. Thus, translational arrest blocks cellular and viral translation.
What competes with Pyrimidine-Tract Binding Protein and what is it competing to do to?
The RNA-binding Motif Protein 4 (RBM4) competes and acts oppositely of the Pyrimidine-Tract Binding Protein (PTB).
The RBM4 and PTB compete for binding to a CU-rich element (CCUUCCUU)
In EJC-dependent nonsense-mediated decay, a termination codon is upstream of an EJC and NMD is stimulated. How does the SURF complex aid to “decay mRNA?”
The SURF complex aids in cleaving the mRNA that has the EJC proteins remaining on it. Because the fragmented ends of the mRNA do not have the protected poly-A tail or the 5’ cap and are exposed, the cleaved ends are now vulnerable to nearby degrading enzymes.
In miRNA post-transcriptional silencing of gene expression, the base pairing between the single-stranded miRNA and its target mRNA directs RISC to do one of two things? What does it direct RISC to do?
The single-stranded miRNA and its target mRNA base pairing direct RISC to either 1) cleave the mRNA target or 2) repress its translation.
If guide and target base-pairing homology in miRNA post-transcriptional silencing of gene expression is high, what happens to the mRNA?
mRNA is degraded by RISC
If guide and target base-paring homology in miRNA post-transcriptional silencing of gene expression is low, what happens?
If homology is low, translation is inhibited.
What are the 3 pathways to deliver goods to the lysosome and what does each of them do specifically?
1) Macroautophagy- engulfment of organelles through an autophagosome vacuole, which then fuses with lysosomes
2) Microautophagy- direct engulfment of proteins through membrane invagination and is then processed by a lysosome
3) Chaperone-Mediated Autophagy-selective degradation of proteins that are targeted and directly translocated across the lysosome membrane for degradation
What are the 3 ubiquitin enzymes that area part of the enzyme cascade in the process of protein ubiquitilation?
E1: ubiquitin-activating enzyme
E2: ubiquitin-conjugating enzyme
E3: ligase-selectively targets proteins for polyubiquitylation
