User:Jeremy C. Caylor/Sandbox 1 - Revision history

Jeremy C. Caylor at 21:02, 26 April 2018

Jeremy C. Caylor — Thu, 26 Apr 2018 21:02:05 GMT

←Older revision		Revision as of 21:02, 26 April 2018
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	==Autoregulation==		==Autoregulation==

-	[[Image:~~Sxl Autoregulation Splicing~~.png\|300 px\|right\|thumb\|Figure 4. Alternative splicing mechanism for autoregulation of Sxl. The presence of Sxl causes the alternative splicing of exon 3 in the female mRNA transcript. The retention of exon 3, along with the premature stop codon it contains, leads to a truncated and inactive Sxl protein in males.]]	+	[[Image:Screen Shot 2018-04-26 at 4.55.49 PM.png\|300 px\|right\|thumb\|Figure 4. Alternative splicing mechanism for autoregulation of Sxl. The presence of Sxl causes the alternative splicing of exon 3 in the female mRNA transcript. The retention of exon 3, along with the premature stop codon it contains, leads to a truncated and inactive Sxl protein in males.]]
	Sxl controls its own levels of expression via positive and negative [https://en.wikipedia.org/wiki/Autoregulation autoregulation]. Sxl binds its own pre-mRNA transcript in a similar manner as its downstream targets, Tra and Msl2. Through binding to its recognition element, Sxl causes a 3’ splice site to be skipped. [https://en.wikipedia.org/wiki/Alternative_splicing Alternative splicing] occurs utilizing a 3’ splice site further downstream, cleaving out a premature stop codon within Exon 3 and preventing truncation and inactivation<ref name="Black" /> (Figure 4). This is a pathway of positive autoregulation, as functional Sxl protein must be present to cause proper processing of the pre-mRNA. The negative autoregulation pathway of Sxl proceeds via repression of its own translation. The Sxl transcript contains the target polyuridine sequence within its 3’UTR. Sxl binds this target, and blocks translation<ref name="Black" />. Negative autoregulation allows maintenance of a stable and standard Sxl protein concentration. An excess of Sxl increases the degree of translation repression because more Sxl protein are present to potentially bind at the 3’UTR, while a shortage allows for more unrepressed translation.		Sxl controls its own levels of expression via positive and negative [https://en.wikipedia.org/wiki/Autoregulation autoregulation]. Sxl binds its own pre-mRNA transcript in a similar manner as its downstream targets, Tra and Msl2. Through binding to its recognition element, Sxl causes a 3’ splice site to be skipped. [https://en.wikipedia.org/wiki/Alternative_splicing Alternative splicing] occurs utilizing a 3’ splice site further downstream, cleaving out a premature stop codon within Exon 3 and preventing truncation and inactivation<ref name="Black" /> (Figure 4). This is a pathway of positive autoregulation, as functional Sxl protein must be present to cause proper processing of the pre-mRNA. The negative autoregulation pathway of Sxl proceeds via repression of its own translation. The Sxl transcript contains the target polyuridine sequence within its 3’UTR. Sxl binds this target, and blocks translation<ref name="Black" />. Negative autoregulation allows maintenance of a stable and standard Sxl protein concentration. An excess of Sxl increases the degree of translation repression because more Sxl protein are present to potentially bind at the 3’UTR, while a shortage allows for more unrepressed translation.

Jeremy C. Caylor at 18:54, 26 April 2018

Jeremy C. Caylor — Thu, 26 Apr 2018 18:54:43 GMT

←Older revision		Revision as of 18:54, 26 April 2018
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	1. Hydrogen bonding with RNA bases:		1. Hydrogen bonding with RNA bases:

-	There are numerous hydrogen bonds between the residues and the nucleotide bases. RRM2 creates three hydrogen bonds with U3 and G4 with residues <scene name='78/782600/H-bond_u3_bases/3'>Asn217 and Arg252</scene> and residue <scene name='78/782600/Ala289_g4/1'>Ala289</scene>. It also forms two hydrogen bonds with U5 with residues <scene name='78/782600/Rrm2_res_hbond_w_bases/4'>Aln239 and Asn212</scene>. RRM1 creates five hydrogen bonds with U6, U7, and U8 with residues <scene name='78/782600/Rrm1_res_h-bond_w_bases/6'>Arg195, Gln134, and Ser165</scene>. It also creates seven hydrogens bonds to U9, U10, and U11 with residues <scene name='78/782600/U9_u10/1'>Gly204, Arg202, Lys197</scene> and residues <scene name='78/782600/U11/1'>Arg155 and Asn126</scene><ref name="Handa" />.	+	There are numerous hydrogen bonds between the residues and the nucleotide bases. RRM2 creates three hydrogen bonds with U3 and G4 with residues <scene name='78/782600/H-bond_u3_bases/3'>Asn217 and Arg252</scene> and residue <scene name='78/782600/Ala289_g4/1'>Ala289</scene>. It also forms two hydrogen bonds with U5 with residues <scene name='78/782600/Rrm2_res_hbond_w_bases/5'>Aln239 and Asn212</scene>. RRM1 creates five hydrogen bonds with U6, U7, and U8 with residues <scene name='78/782600/Rrm1_res_h-bond_w_bases/6'>Arg195, Gln134, and Ser165</scene>. It also creates seven hydrogens bonds to U9, U10, and U11 with residues <scene name='78/782600/U9_u10/1'>Gly204, Arg202, Lys197</scene> and residues <scene name='78/782600/U11/1'>Arg155 and Asn126</scene><ref name="Handa" />.

	2. Hydrogen bonding with the RNA backbone:		2. Hydrogen bonding with the RNA backbone:

Jeremy C. Caylor at 18:48, 26 April 2018

Jeremy C. Caylor — Thu, 26 Apr 2018 18:48:00 GMT

←Older revision		Revision as of 18:48, 26 April 2018
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	1. Hydrogen bonding with RNA bases:		1. Hydrogen bonding with RNA bases:

-	There are numerous hydrogen bonds between the residues and the nucleotide bases. RRM2 creates three hydrogen bonds with U3 and G4 with residues <scene name='78/782600/H-bond_u3_bases/3'>Asn217 and Arg252</scene> and residue <scene name='78/782600/Ala289_g4/1'>Ala289</scene>. It also forms two hydrogen bonds with U5 with residues <scene name='78/782600/Rrm2_res_hbond_w_bases/4'>Aln239 and Asn212</scene>. RRM1 creates ~~four~~ hydrogen bonds with U6, U7, and U8 with residues <scene name='78/782600/Rrm1_res_h-bond_w_bases/6'>Arg195, Gln134, and Ser165</scene>. It also creates seven hydrogens bonds to U9, U10, and U11 with residues <scene name='78/782600/U9_u10/1'>Gly204, Arg202, Lys197</scene> and residues <scene name='78/782600/U11/1'>Arg155 and Asn126</scene><ref name="Handa" />.	+	There are numerous hydrogen bonds between the residues and the nucleotide bases. RRM2 creates three hydrogen bonds with U3 and G4 with residues <scene name='78/782600/H-bond_u3_bases/3'>Asn217 and Arg252</scene> and residue <scene name='78/782600/Ala289_g4/1'>Ala289</scene>. It also forms two hydrogen bonds with U5 with residues <scene name='78/782600/Rrm2_res_hbond_w_bases/4'>Aln239 and Asn212</scene>. RRM1 creates five hydrogen bonds with U6, U7, and U8 with residues <scene name='78/782600/Rrm1_res_h-bond_w_bases/6'>Arg195, Gln134, and Ser165</scene>. It also creates seven hydrogens bonds to U9, U10, and U11 with residues <scene name='78/782600/U9_u10/1'>Gly204, Arg202, Lys197</scene> and residues <scene name='78/782600/U11/1'>Arg155 and Asn126</scene><ref name="Handa" />.

	2. Hydrogen bonding with the RNA backbone:		2. Hydrogen bonding with the RNA backbone:

Jeremy C. Caylor at 18:42, 26 April 2018

Jeremy C. Caylor — Thu, 26 Apr 2018 18:42:41 GMT

←Older revision		Revision as of 18:42, 26 April 2018
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	==Autoregulation==		==Autoregulation==

-	[[Image:Sxl Autoregulation Splicing.png\|300 px\|right\|thumb\|Figure 4. Alternative splicing mechanism for autoregulation of Sxl. The presence of Sxl causes the alternative splicing of exon 3 in the female mRNA transcript. The retention of exon 3, along with the premature stop codon it contains, leads to a truncated, inactive Sxl protein in males.]]	+	[[Image:Sxl Autoregulation Splicing.png\|300 px\|right\|thumb\|Figure 4. Alternative splicing mechanism for autoregulation of Sxl. The presence of Sxl causes the alternative splicing of exon 3 in the female mRNA transcript. The retention of exon 3, along with the premature stop codon it contains, leads to a truncated and inactive Sxl protein in males.]]
	Sxl controls its own levels of expression via positive and negative [https://en.wikipedia.org/wiki/Autoregulation autoregulation]. Sxl binds its own pre-mRNA transcript in a similar manner as its downstream targets, Tra and Msl2. Through binding to its recognition element, Sxl causes a 3’ splice site to be skipped. [https://en.wikipedia.org/wiki/Alternative_splicing Alternative splicing] occurs utilizing a 3’ splice site further downstream, cleaving out a premature stop codon within Exon 3 and preventing truncation and inactivation<ref name="Black" /> (Figure 4). This is a pathway of positive autoregulation, as functional Sxl protein must be present to cause proper processing of the pre-mRNA. The negative autoregulation pathway of Sxl proceeds via repression of its own translation. The Sxl transcript contains the target polyuridine sequence within its 3’UTR. Sxl binds this target, and blocks translation<ref name="Black" />. Negative autoregulation allows maintenance of a stable and standard Sxl protein concentration. An excess of Sxl increases the degree of translation repression because more Sxl protein are present to potentially bind at the 3’UTR, while a shortage allows for more unrepressed translation.		Sxl controls its own levels of expression via positive and negative [https://en.wikipedia.org/wiki/Autoregulation autoregulation]. Sxl binds its own pre-mRNA transcript in a similar manner as its downstream targets, Tra and Msl2. Through binding to its recognition element, Sxl causes a 3’ splice site to be skipped. [https://en.wikipedia.org/wiki/Alternative_splicing Alternative splicing] occurs utilizing a 3’ splice site further downstream, cleaving out a premature stop codon within Exon 3 and preventing truncation and inactivation<ref name="Black" /> (Figure 4). This is a pathway of positive autoregulation, as functional Sxl protein must be present to cause proper processing of the pre-mRNA. The negative autoregulation pathway of Sxl proceeds via repression of its own translation. The Sxl transcript contains the target polyuridine sequence within its 3’UTR. Sxl binds this target, and blocks translation<ref name="Black" />. Negative autoregulation allows maintenance of a stable and standard Sxl protein concentration. An excess of Sxl increases the degree of translation repression because more Sxl protein are present to potentially bind at the 3’UTR, while a shortage allows for more unrepressed translation.

Jeremy C. Caylor at 18:41, 26 April 2018

Jeremy C. Caylor — Thu, 26 Apr 2018 18:41:18 GMT

←Older revision		Revision as of 18:41, 26 April 2018
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	==Autoregulation==		==Autoregulation==

-	[[Image:Sxl Autoregulation Splicing.png\|300 px\|right\|thumb\|Figure 4. Alternative splicing mechanism for autoregulation of Sxl. The presence of Sxl causes the ~~inclusion~~ of exon 3 in the female mRNA transcript. ~~Exon~~ 3 ~~is alternatively spliced~~ in ~~male mRNA transcripts~~.]]	+	[[Image:Sxl Autoregulation Splicing.png\|300 px\|right\|thumb\|Figure 4. Alternative splicing mechanism for autoregulation of Sxl. The presence of Sxl causes the alternative splicing of exon 3 in the female mRNA transcript. The retention of exon 3, along with the premature stop codon it contains, leads to a truncated, inactive Sxl protein in males.]]
	Sxl controls its own levels of expression via positive and negative [https://en.wikipedia.org/wiki/Autoregulation autoregulation]. Sxl binds its own pre-mRNA transcript in a similar manner as its downstream targets, Tra and Msl2. Through binding to its recognition element, Sxl causes a 3’ splice site to be skipped. [https://en.wikipedia.org/wiki/Alternative_splicing Alternative splicing] occurs utilizing a 3’ splice site further downstream, cleaving out a premature stop codon within Exon 3 and preventing truncation and inactivation<ref name="Black" /> (Figure 4). This is a pathway of positive autoregulation, as functional Sxl protein must be present to cause proper processing of the pre-mRNA. The negative autoregulation pathway of Sxl proceeds via repression of its own translation. The Sxl transcript contains the target polyuridine sequence within its 3’UTR. Sxl binds this target, and blocks translation<ref name="Black" />. Negative autoregulation allows maintenance of a stable and standard Sxl protein concentration. An excess of Sxl increases the degree of translation repression because more Sxl protein are present to potentially bind at the 3’UTR, while a shortage allows for more unrepressed translation.		Sxl controls its own levels of expression via positive and negative [https://en.wikipedia.org/wiki/Autoregulation autoregulation]. Sxl binds its own pre-mRNA transcript in a similar manner as its downstream targets, Tra and Msl2. Through binding to its recognition element, Sxl causes a 3’ splice site to be skipped. [https://en.wikipedia.org/wiki/Alternative_splicing Alternative splicing] occurs utilizing a 3’ splice site further downstream, cleaving out a premature stop codon within Exon 3 and preventing truncation and inactivation<ref name="Black" /> (Figure 4). This is a pathway of positive autoregulation, as functional Sxl protein must be present to cause proper processing of the pre-mRNA. The negative autoregulation pathway of Sxl proceeds via repression of its own translation. The Sxl transcript contains the target polyuridine sequence within its 3’UTR. Sxl binds this target, and blocks translation<ref name="Black" />. Negative autoregulation allows maintenance of a stable and standard Sxl protein concentration. An excess of Sxl increases the degree of translation repression because more Sxl protein are present to potentially bind at the 3’UTR, while a shortage allows for more unrepressed translation.

Jeremy C. Caylor at 00:47, 26 April 2018

Jeremy C. Caylor — Thu, 26 Apr 2018 00:47:40 GMT

←Older revision		Revision as of 00:47, 26 April 2018
Line 30:		Line 30:
	==Autoregulation==		==Autoregulation==

-	[[Image:Sxl Autoregulation Splicing.png\|300 px\|right\|thumb\|Figure 4. Alternative splicing mechanism for autoregulation of Sxl. The presence of Sxl causes the inclusion of exon 3 in the female mRNA transcript. Exon ~~three~~ is alternatively spliced in male mRNA transcripts.]]	+	[[Image:Sxl Autoregulation Splicing.png\|300 px\|right\|thumb\|Figure 4. Alternative splicing mechanism for autoregulation of Sxl. The presence of Sxl causes the inclusion of exon 3 in the female mRNA transcript. Exon 3 is alternatively spliced in male mRNA transcripts.]]
	Sxl controls its own levels of expression via positive and negative [https://en.wikipedia.org/wiki/Autoregulation autoregulation]. Sxl binds its own pre-mRNA transcript in a similar manner as its downstream targets, Tra and Msl2. Through binding to its recognition element, Sxl causes a 3’ splice site to be skipped. [https://en.wikipedia.org/wiki/Alternative_splicing Alternative splicing] occurs utilizing a 3’ splice site further downstream, cleaving out a premature stop codon within Exon 3 and preventing truncation and inactivation<ref name="Black" /> (Figure 4). This is a pathway of positive autoregulation, as functional Sxl protein must be present to cause proper processing of the pre-mRNA. The negative autoregulation pathway of Sxl proceeds via repression of its own translation. The Sxl transcript contains the target polyuridine sequence within its 3’UTR. Sxl binds this target, and blocks translation<ref name="Black" />. Negative autoregulation allows maintenance of a stable and standard Sxl protein concentration. An excess of Sxl increases the degree of translation repression because more Sxl protein are present to potentially bind at the 3’UTR, while a shortage allows for more unrepressed translation.		Sxl controls its own levels of expression via positive and negative [https://en.wikipedia.org/wiki/Autoregulation autoregulation]. Sxl binds its own pre-mRNA transcript in a similar manner as its downstream targets, Tra and Msl2. Through binding to its recognition element, Sxl causes a 3’ splice site to be skipped. [https://en.wikipedia.org/wiki/Alternative_splicing Alternative splicing] occurs utilizing a 3’ splice site further downstream, cleaving out a premature stop codon within Exon 3 and preventing truncation and inactivation<ref name="Black" /> (Figure 4). This is a pathway of positive autoregulation, as functional Sxl protein must be present to cause proper processing of the pre-mRNA. The negative autoregulation pathway of Sxl proceeds via repression of its own translation. The Sxl transcript contains the target polyuridine sequence within its 3’UTR. Sxl binds this target, and blocks translation<ref name="Black" />. Negative autoregulation allows maintenance of a stable and standard Sxl protein concentration. An excess of Sxl increases the degree of translation repression because more Sxl protein are present to potentially bind at the 3’UTR, while a shortage allows for more unrepressed translation.

Jeremy C. Caylor at 00:40, 26 April 2018

Jeremy C. Caylor — Thu, 26 Apr 2018 00:40:26 GMT

←Older revision		Revision as of 00:40, 26 April 2018
Line 20:		Line 20:
	2. Hydrogen bonding with the RNA backbone:		2. Hydrogen bonding with the RNA backbone:

-	There is an unusual abundance of interactions between the protein and the RNA backbone of the ligand. RRM2 residues <scene name='78/782600/U9_u6_u3_backbone_h_bonds/1'>Tyr214, Asn241, Arg252, Arg258</scene> hydrogen bond to the backbone of U3, U6 and U9. RRM1 residues <scene name='78/782600/Rrm1_h_bond_to_u9_u11_backbone/1'>Asn130 and Arg155</scene><ref name="Handa" /> hydrogen bond to the backbone of U9 and U11.	+	There are an unusual abundance of interactions between the protein and the RNA backbone of the ligand. RRM2 residues <scene name='78/782600/U9_u6_u3_backbone_h_bonds/1'>Tyr214, Asn241, Arg252, Arg258</scene> hydrogen bond to the backbone of U3, U6 and U9. RRM1 residues <scene name='78/782600/Rrm1_h_bond_to_u9_u11_backbone/1'>Asn130 and Arg155</scene><ref name="Handa" /> hydrogen bond to the backbone of U9 and U11.

	3. Intermolecular stacking:		3. Intermolecular stacking:
		+
	[https://en.wikipedia.org/wiki/Stacking_(chemistry) Intermolecular stacking] between the aromatic side chains and the nucleotide bases also contributes to RNA binding. In RRM2, U3-G4-U5 stack with <scene name='78/782600/Rrm2_residues_stacking/4'>V254, Y214, and F256</scene> respectively. In RRM1, residues <scene name='78/782600/Rrm1_intermolecular_stacking/4'>Y131, R195, N130, F170</scene> are involved in favorable intermolecular stacking of aromatic rings with nucleotides U6-U11<ref name="Handa" />.		[https://en.wikipedia.org/wiki/Stacking_(chemistry) Intermolecular stacking] between the aromatic side chains and the nucleotide bases also contributes to RNA binding. In RRM2, U3-G4-U5 stack with <scene name='78/782600/Rrm2_residues_stacking/4'>V254, Y214, and F256</scene> respectively. In RRM1, residues <scene name='78/782600/Rrm1_intermolecular_stacking/4'>Y131, R195, N130, F170</scene> are involved in favorable intermolecular stacking of aromatic rings with nucleotides U6-U11<ref name="Handa" />.

Jeremy C. Caylor at 00:39, 26 April 2018

Jeremy C. Caylor — Thu, 26 Apr 2018 00:39:36 GMT

←Older revision		Revision as of 00:39, 26 April 2018
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	2. Hydrogen bonding with the RNA backbone:		2. Hydrogen bonding with the RNA backbone:

-	There is an unusual abundance of interactions between the protein and the RNA backbone of the ligand. ~~Residues~~ <scene name='78/782600/U9_u6_u3_backbone_h_bonds/1'>Tyr214, Asn241, Arg252, Arg258</scene> hydrogen bond to the backbone of U3, U6 and U9. ~~Residues~~ <scene name='78/782600/Rrm1_h_bond_to_u9_u11_backbone/1'>Asn130 and Arg155</scene><ref name="Handa" /> hydrogen bond to the backbone of U9 and U11.	+	There is an unusual abundance of interactions between the protein and the RNA backbone of the ligand. RRM2 residues <scene name='78/782600/U9_u6_u3_backbone_h_bonds/1'>Tyr214, Asn241, Arg252, Arg258</scene> hydrogen bond to the backbone of U3, U6 and U9. RRM1 residues <scene name='78/782600/Rrm1_h_bond_to_u9_u11_backbone/1'>Asn130 and Arg155</scene><ref name="Handa" /> hydrogen bond to the backbone of U9 and U11.

	3. Intermolecular stacking:		3. Intermolecular stacking:

Jeremy C. Caylor at 19:51, 25 April 2018

Jeremy C. Caylor — Wed, 25 Apr 2018 19:51:35 GMT

←Older revision		Revision as of 19:51, 25 April 2018
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	== Mutation ==		== Mutation ==
-	In fruit flies, [https://en.wikipedia.org/wiki/Dosage_compensation dosage compensation] is achieved by hyperexpression of the single X chromosome found in the male genome. The single X chromosome is hyperexpressed and regulated by a group of genes known as the Male-specific lethal genes. The genes ~~involve~~ work together to produce a complex known as the Male-specific lethal complex (Msl complex). One gene that is important in forming this complex is the gene that codes for the Msl-2 protein. Without this protein, the Msl complex cannot form <ref name="Penalva">Penalva L, Sanchez L. RNA Binding Protein Sex-Lethal (Sxl) and Control of Drosophila Sex Determination and Dosage Compensation. Microbiol Mol Biol Rev.;67(3):343-356. [http://mmbr.asm.org/content/67/3/343.short doi: 10.1128/MMBR.67.3.343–359.2003]</ref>. Males exclusively make the Msl-2 protein and therefore exclusively create the Msl complex. ~~Female~~ cannot make the complex because the Sxl protein prevents the production of the Msl-2 protein. It ~~prevents the protein formation~~ by alternatively splicing of an intron near the 5’ UTR. In males this intron is included and in females it is not. <ref name="Penalva" /> Mutations of the Sxl protein can affect the formation of this complex and lead to death for females—hence the name sex lethal. If the Sxl gene is mutated in females, the formation of the Msl-2 complex will not be inhibited. If there is a functional Msl-2 complex in females then both of the X chromosomes will be hyperexpressed <ref name="Penalva" /> The overexpression of genes on the X chromosome is a fatal phenomenon ultimately caused by a mutation of the Sxl protein. Although a mutation to the Sxl gene is harmful to females, it has no effect on males because the functional Sxl gene is not expressed—a mutation in males has no phenotypic effect.	+	In fruit flies, [https://en.wikipedia.org/wiki/Dosage_compensation dosage compensation] is achieved by hyperexpression of the single X chromosome found in the male genome. The single X chromosome is hyperexpressed and regulated by a group of genes known as the Male-specific lethal genes. The genes involved work together to produce a complex known as the Male-specific lethal complex (Msl complex). One gene that is important in forming this complex is the gene that codes for the Msl-2 protein. Without this protein, the Msl complex cannot form <ref name="Penalva">Penalva L, Sanchez L. RNA Binding Protein Sex-Lethal (Sxl) and Control of Drosophila Sex Determination and Dosage Compensation. Microbiol Mol Biol Rev.;67(3):343-356. [http://mmbr.asm.org/content/67/3/343.short doi: 10.1128/MMBR.67.3.343–359.2003]</ref>. Males exclusively make the Msl-2 protein and therefore exclusively create the Msl complex. Females cannot make the complex because the Sxl protein prevents the production of the Msl-2 protein. It does this by alternatively splicing an intron near the 5’ UTR. In males this intron is included and in females it is not <ref name="Penalva" />. Mutations of the Sxl protein can affect the formation of this complex and lead to death for females—hence the name sex lethal. If the Sxl gene is mutated in females, the formation of the Msl-2 complex will not be inhibited. If there is a functional Msl-2 complex in females then both of the X chromosomes will be hyperexpressed <ref name="Penalva" />. The overexpression of genes on the X chromosome is a fatal phenomenon ultimately caused by a mutation of the Sxl protein. Although a mutation to the Sxl gene is harmful to females, it has no effect on males because the functional Sxl gene is not expressed—a mutation in males has no phenotypic effect.

	== References ==		== References ==
	<references/>		<references/>

Jeremy C. Caylor at 19:48, 25 April 2018

Jeremy C. Caylor — Wed, 25 Apr 2018 19:48:02 GMT

←Older revision		Revision as of 19:48, 25 April 2018
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	== Introduction ==		== Introduction ==
	[[Image:Sxl function 2018-03-27 at 2.41.00 PM.png\|500 px\|right\|thumb\|Figure 1. Sxl sex determination and dosage compensation pathways. Functionality of Sxl is determined by the number of X chromosomes. The functional protein (XX) causes a cascade that leads to female structures and behaviors, while the nonfunctional protein results in the default male structures and behaviors.]]Sex lethal (Sxl) is an [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] that plays a vital role in sex determination and dosage compensation in ''[https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]'', the common fruit fly <ref name="Black">doi: 10.1146/annurev.biochem.72.121801.161720</ref>. Sxl binds specifically to the continuous single-stranded RNA sequence 5’-UGUUUUUUU <ref name="Handa">doi:10.1038/19242		[[Image:Sxl function 2018-03-27 at 2.41.00 PM.png\|500 px\|right\|thumb\|Figure 1. Sxl sex determination and dosage compensation pathways. Functionality of Sxl is determined by the number of X chromosomes. The functional protein (XX) causes a cascade that leads to female structures and behaviors, while the nonfunctional protein results in the default male structures and behaviors.]]Sex lethal (Sxl) is an [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] that plays a vital role in sex determination and dosage compensation in ''[https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]'', the common fruit fly <ref name="Black">doi: 10.1146/annurev.biochem.72.121801.161720</ref>. Sxl binds specifically to the continuous single-stranded RNA sequence 5’-UGUUUUUUU <ref name="Handa">doi:10.1038/19242
-	</ref>. Functional copies of Sxl are expressed only in female fruit flies, where they induce sex-specific splicing patterns in the transcript of the ''[https://en.wikipedia.org/wiki/Transformer_(gene) Transformer]'' (Tra) gene that lead to its function. Tra initiates a cascade pathway that results in the development of female structures and behaviors (Figure 1). 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 ''[https://www.wikigenes.org/e/gene/e/33565.html Male-specific lethal 2]'' (Msl-2) is the downstream target through which Sxl regulates dosage compensation. Active Sxl protein (in females) binds to two recognition elements on Msl-2 causing the retention of the first intron in the 5’UTR of Msl-2. Sxl protein bound at this intron then blocks translation, preventing expression of Msl-2 in females <ref name="Black" />. ~~Without~~ Msl-2 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> (Figure 1).	+	</ref>. Functional copies of Sxl are expressed only in female fruit flies, where they induce sex-specific splicing patterns in the transcript of the ''[https://en.wikipedia.org/wiki/Transformer_(gene) Transformer]'' (Tra) gene that lead to its function. Tra initiates a cascade pathway that results in the development of female structures and behaviors (Figure 1). 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 ''[https://www.wikigenes.org/e/gene/e/33565.html Male-specific lethal 2]'' (Msl-2) is the downstream target through which Sxl regulates dosage compensation. Active Sxl protein (in females) binds to two recognition elements on Msl-2 causing the retention of the first intron in the 5’UTR of Msl-2. Sxl protein bound at this intron then blocks translation, preventing expression of Msl-2 in females <ref name="Black" />. With no Msl-2 protein present, 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> (Figure 1).