Question 11 [20 marks / 20 minutes] This question is about mechanisms of gene re
ID: 279447 • Letter: Q
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Question 11 [20 marks / 20 minutes] This question is about mechanisms of gene regulation in eukaryotes. a) In Drosophila melanogaster, Sex-lethal (Sx) controls somatic sexual development. i. Describe the regulatory mechanism that leads to the presence of Sxl protein only in female early embryos. Explain how this difference is maintained later in the life cycle 4 marks] 6 marks] ii. b) List two RNA modifications present in eukaryotes. Describe in detail the function of one of these RNA modifications in a living cell. 6 marks] c) Describe the function of two different DNA and/or histone modifications present in eukaryotes. [4 marks]Explanation / Answer
a i. The sex lethal gene expression depends on X:A signal. X:A signal is important to chose the sexual pathway and balance the dosage compensation. X:A signal decides the the state of activity of Sxl around the blastoderm stage. Once this is achieved, the X:A signal is no longer needed and the activity of Sxl remains fixed. X:A signal is constituted by proteins of the basic helix-loop-helix family. They form heteromeric complexes that can function as important regulators of the early Sxl promoter. Following the blastoderm stage, Sxl expression in females is maintained by a positive autoregulatory loop such that Sxl positively controls its own expression. These Sxl mutant alleles do not need the maternal Daughterless product for their expression in the zygote. They act in trans Icausing the activation of a wild-type Sxl+ allele in the absence of the maternal Daughterless product . SxL gene controls the splicing of Sxl ,tra , msl2 genes. It also controls the stability of msl2 genes. Based on the differential mRNA transcripts, one can decide on the sexuality of the organism as well.
II. The late female-specific and male-specific mRNAs are expressed from a promoter, SxlPm, also called maintenance from the cellular blastoderm stage through adulthood. Although these transcripts all have a common 5? exon (exon L1), they are sex-specifically spliced to produce mRNAs with different coding potentials. In females, the third exon is skipped to generate protein encoding mRNAs. Structural differences arises due to alternative polyadenylation or alternate splicingom alternative splicing. SXL function also depends on cross talk between proteins bound at different sites to maintain the gene in the life cycle.
b.m6A or 7 methyl adenosine at 5' end and A tailing in mRNA are two RNA modifications. Apart from that several other modifications include pseuouridylation etc. m6A modification improves the half life of mRNA i.e improved stability, affect protein translation and localization and plays an essential role in stem cell pluripotency (importance in neural stem cell renewal, cell proliferation and differntiation)
c. DNA modifications are predominantly called epigenetic modifications (chromatin modification). DNA methylation by methyltransferases (role in type 2 diabetes) are involved in gene regulation, recruitment of protein complexes such as MecP2, cross talks with other post translational modifications, RNA splicing, genome organization, nuclear architecture etc. Another important Histone modification is acetylation by acetylase which is also known to regulate many processes such as gene regulation or deacetylation by HDACs known to play an important role say in repression of muscle differentiation etc.
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