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MBB331_Week11-Fall-2011

2 drosophila female specific sxl sex lethal splicing

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Unformatted text preview: ogical roles, for alternative example differences in splicing of a cascade of gene products in Drosophila are used in sex determination: one set of splicing events leads to male fly, one set to female fly set 21 ALTERNATIVE SPLICING ALTERNATIVE Weaver 2002 Molecular Biology Ed. 2 • Drosophila female-specific Sxl (sex lethal) splicing leads to Sxl female-specific tra (transformer) splicing, which leads to tra female-specific dsx (doublesex) splicing that ultimately dsx produces protein inactivating male-specific genes produces • Male-specific splicing ---> inactive products ---> default is Male-specific male male • SR proteins control alternate splicing-Sxl, Tra and Tra-2 are SR 22 SR proteins that contribute to female-specific splices SR ALTERNATIVE SPLICING ALTERNATIVE -recall that Drosophila P elements also undergo alternative splicing 23 ALTERNATIVE SPLICING ALTERNATIVE -an extreme example of the protein diversity that can be generated by alternative splicing is the Drosophila Dscam locus, which can be variably spliced to encode 152,064 possible transmembrane proteins -mediates self-recognition of neurons by homophilic interactions between matching Dscam molecules 24 REGULATION OF GENE REGULATION EXPRESSION AT mRNA LEVEL EXPRESSION Prokaryotes: Prokaryotes: • (i) Regulation by mRNA cleavage • (ii) Control at translation • (iii) Regulation of mRNA by antisense (iii) RNA RNA 25 (i) Regulation by mRNA cleavage: T7 and λ RNA λ T7 -phage T7: polycistronic mRNA cleaved into -phage mRNAs for individual genes - T7 early region 6 cistrons cleaved by RNase III at hairpin “bubbles” at intercistronic sites to release 5 RNAs (4 monocistronic and 1 bicistronic) RNAs Lewin Genes VII 2000 Oxford University Press 26 (i) Regulation by mRNA cleavage: T7 and λ RNA λ T7 -cleavage at end of 1.2 ORF in the T7 -cleavage transcript required for translation of the bicistronic 1.1/1.2 mRNA 1.1/1.2 -if cleavage prevented, the resulting longer -if mRNA adopts a secondary structure that prevents translation initiation at 1.1 ORF 1.1 Lewin Genes VII 2000 Oxford University Press 27 (i) Regulation by mRNA cleavage: T7 and λ RNA λ T7 -λ mRNA with int ORF not normally translated, but mutations in sib site sib downstream of int enable Int protein to be made made -sib mutation prevents RNase III from recognizing mRNA cleavage site that normally release 3´end for degradation normally Lewin Genes VII 2000 Oxford University Press 28 ii) TRANSLATIONAL CONTROL: REVIEW OF TRANSLATION INITIATION IN PROKARYOTES REVIEW OF TRANSLATION INITIATION IN PROKARYOTES ...
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