User:Jeremy C. Caylor/Sandbox 1
From Proteopedia
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</ref>. Functional copies of Sxl are expressed only in female fruit flies, where they induce sex-specific splicing patterns in the transcript of the Transformer (Tra) gene that lead to its function. Tra initiates a cascade that results in the development of female structures and behaviors. Sxl binds to its recognition element in the Tra pre-mRNA transcript, thereby blocking association of the splicing factor U2AF at the nearby splice site. Without the association of this essential splicing factor, the 3’ splice site shifts downstream, causing the removal of a premature stop codon and preventing truncation and inactivation of the Tra protein <ref name="Black" />. The pre-mRNA transcript of Male-specific lethal 2 (Msl2) is the downstream target through which Sxl regulates dosage compensation. Active Sxl protein (in females) binds to two recognition elements on Msl2 causing the retention of the first intron in the 5’UTR of Msl2. Sxl bound at this intron then blocks translation, preventing expression of Msl2 in females <ref name="Black" />. Without Msl2 protein, the Male specific lethal complex cannot form and carry out its function of upregulating expression of genes on the X chromosome <ref name="dosage">Georgiev P, Chlamydas S, Akhtar A. Drosophila dosage compensation. Fly 2011; 5(2):147-154. https://doi.org/10.4161/fly.5.2.14934</ref>. | </ref>. Functional copies of Sxl are expressed only in female fruit flies, where they induce sex-specific splicing patterns in the transcript of the Transformer (Tra) gene that lead to its function. Tra initiates a cascade that results in the development of female structures and behaviors. Sxl binds to its recognition element in the Tra pre-mRNA transcript, thereby blocking association of the splicing factor U2AF at the nearby splice site. Without the association of this essential splicing factor, the 3’ splice site shifts downstream, causing the removal of a premature stop codon and preventing truncation and inactivation of the Tra protein <ref name="Black" />. The pre-mRNA transcript of Male-specific lethal 2 (Msl2) is the downstream target through which Sxl regulates dosage compensation. Active Sxl protein (in females) binds to two recognition elements on Msl2 causing the retention of the first intron in the 5’UTR of Msl2. Sxl bound at this intron then blocks translation, preventing expression of Msl2 in females <ref name="Black" />. Without Msl2 protein, the Male specific lethal complex cannot form and carry out its function of upregulating expression of genes on the X chromosome <ref name="dosage">Georgiev P, Chlamydas S, Akhtar A. Drosophila dosage compensation. Fly 2011; 5(2):147-154. https://doi.org/10.4161/fly.5.2.14934</ref>. | ||
| - | <StructureSection load='1B7F' size='350' side='right' caption='Sex lethal (PDB: 1B7F)' scene='78/782600/Opening_image/1'> | ||
| - | == Structure == | + | ==Structure== |
| + | <StructureSection load='1B7F' size='350' side='right' caption='Sex lethal (PDB: 1B7F)' scene='78/782600/Opening_image/1'> | ||
===RRMs=== | ===RRMs=== | ||
The sex-lethal protein (Sxl) is 354 amino acid residues long. It is composed of two highly conserved regions called RNA recognition motifs (RRMs) that function as a monomeric unit. Each RRM is approximately 90 amino acids long with a four stranded β-pleated sheet and two α-helices. The β-pleated sheets from each RRM interact with the RNA ligand, while the α-helices interact with each other to shape the protein.CLERY Only two interactions between the two RRMs have been observed: between the side chain of Lys 197 and the main chain carbonyl of Val 238 and the side chains of Tyr 131 and Gln 239. The presence of two RRMs increases RNA binding specificity by allowing for an elongated and continuous binding site.CLERY The two RRMs are connected via an interdomain linker. The linker often forms a short 310 α-helix from Gly205 to Thr211.The interaction between the RRMs and the ligand is facilitated by the v-shaped cleft formed by the β-pleated sheet of each RRM. The v-shaped cleft is strongly electropositive which also assists in ligand binding.HANDA | The sex-lethal protein (Sxl) is 354 amino acid residues long. It is composed of two highly conserved regions called RNA recognition motifs (RRMs) that function as a monomeric unit. Each RRM is approximately 90 amino acids long with a four stranded β-pleated sheet and two α-helices. The β-pleated sheets from each RRM interact with the RNA ligand, while the α-helices interact with each other to shape the protein.CLERY Only two interactions between the two RRMs have been observed: between the side chain of Lys 197 and the main chain carbonyl of Val 238 and the side chains of Tyr 131 and Gln 239. The presence of two RRMs increases RNA binding specificity by allowing for an elongated and continuous binding site.CLERY The two RRMs are connected via an interdomain linker. The linker often forms a short 310 α-helix from Gly205 to Thr211.The interaction between the RRMs and the ligand is facilitated by the v-shaped cleft formed by the β-pleated sheet of each RRM. The v-shaped cleft is strongly electropositive which also assists in ligand binding.HANDA | ||
Revision as of 13:38, 28 March 2018
Contents |
Sex Lethal
Introduction
Sex lethal (Sxl) is an RNA-binding protein that plays a vital role in sex determination and dosage compensation in Drosophila melanogaster, the common fruit fly [1]. Sxl binds specifically to the continuous single-stranded RNA sequence 5’-UGUUUUUUU [2]. Functional copies of Sxl are expressed only in female fruit flies, where they induce sex-specific splicing patterns in the transcript of the Transformer (Tra) gene that lead to its function. Tra initiates a cascade that results in the development of female structures and behaviors. Sxl binds to its recognition element in the Tra pre-mRNA transcript, thereby blocking association of the splicing factor U2AF at the nearby splice site. Without the association of this essential splicing factor, the 3’ splice site shifts downstream, causing the removal of a premature stop codon and preventing truncation and inactivation of the Tra protein [1]. The pre-mRNA transcript of Male-specific lethal 2 (Msl2) is the downstream target through which Sxl regulates dosage compensation. Active Sxl protein (in females) binds to two recognition elements on Msl2 causing the retention of the first intron in the 5’UTR of Msl2. Sxl bound at this intron then blocks translation, preventing expression of Msl2 in females [1]. Without Msl2 protein, the Male specific lethal complex cannot form and carry out its function of upregulating expression of genes on the X chromosome [3].
Structure
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Mutation
References
- ↑ 1.0 1.1 1.2 Black DL. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. 2003;72:291-336. doi: 10.1146/annurev.biochem.72.121801.161720., Epub 2003 Feb 27. PMID:12626338 doi:http://dx.doi.org/10.1146/annurev.biochem.72.121801.161720
- ↑ Handa N, Nureki O, Kurimoto K, Kim I, Sakamoto H, Shimura Y, Muto Y, Yokoyama S. Structural basis for recognition of the tra mRNA precursor by the Sex-lethal protein. Nature. 1999 Apr 15;398(6728):579-85. PMID:10217141 doi:10.1038/19242
- ↑ Georgiev P, Chlamydas S, Akhtar A. Drosophila dosage compensation. Fly 2011; 5(2):147-154. https://doi.org/10.4161/fly.5.2.14934
