Problem 16
Competing endogenous RNAs act as molecular "sponges." What does this mean, and what do they compete with?
Problem 18
How are mRNAs stored within the cell in a translationally inactive state, and how can their translation be stimulated?
Problem 19
How and why are eukaryotic mRNAs transported and localized to discrete regions of the cell?
Problem 20
How is it possible that a given mRNA in a cell is found throughout the cytoplasm but the protein that it encodes is only found in a few specific regions?
Problem 21
How may the covalent modification of a protein with a phosphate group alter its function?
Problem 22
What role do ubiquitin ligases play in the regulation of gene expression?
Problem 23
The proteasome is a multi-subunit machine that unfolds and degrades proteins. How is its activity regulated such that it only degrades certain proteins?
Problem 24
In this chapter, we discussed several specific cis-elements in mRNAs that regulate splicing, stability, decay, localization, and translation. However, it is likely that many other uncharacterized cis-elements exist. One way in which they may be characterized is through the use of a reporter gene such as the gene encoding the green fluorescent protein (GFP) from jellyfish. GFP emits green fluorescence when excited by blue light. Explain how one might be able to devise an assay to test for the effect of various cis-elements on posttranscriptional gene regulation using cells that transcribe a GFP mRNA with genetically inserted cis-elements.
Problem 25
Incorrectly spliced RNAs often lead to human pathologies. Scientists have examined cancer cells for splice-specific changes and found that many of the changes disrupt tumor-suppressor gene function [Xu and Lee (2003). Nucl. Acids Res. 31:5635- 5643]\(.\) In general, what would be the effects of splicing changes on these RNAs and the function of tumor-suppressor gene function? How might loss of splicing specificity be associated with cancer?
Problem 26
Mutations in the low-density lipoprotein receptor (LDLR) gene are a primary cause of familial hypercholesterolemia. One such mutation is a SNP in exon 12 of the \(L D L R .\) In premenopausal women, but not in men or postmenopausal women, this SNP leads to skipping of exon 12 and production of a truncated nonfunctional protein. It is hypothesized that this SNP compromises a splice enhancer [Zhu et al. (2007). Hum Mol Genet. \(16: 1765-1772\) ]. What are some possible ways in which this SNP can lead to this defect, but only in premenopausal women?
