Srp20-Human Alternative Splicing Factor: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Neel Bhagat (talk | contribs) No edit summary |
Neel Bhagat (talk | contribs) No edit summary |
||
| Line 33: | Line 33: | ||
=== SR Domain === | === SR Domain === | ||
While the RNA-protein interaction occurs at the RRMs, SR domains are typically responsible for the recruitment of other proteins that act in the splicing mechanism. The serines within the SR domain are phosphorylated by kinases within the cell to direct them to pre-mRNA sites | While the RNA-protein interaction occurs at the RRMs, SR domains are typically responsible for the recruitment of other proteins that act in the splicing mechanism. The serines within the SR domain are phosphorylated by kinases within the cell to direct them to pre-mRNA sites. Phosphorylation acts as recruiting tools for the SRp20 protein and other SR proteins to promote splicing. However, some SR proteins have shown that phosphorylation actually leads to a decrease in splicing, as in the [https://www.ncbi.nlm.nih.gov/pubmed/14765198 SRp38] protein undergoing heat shock. Research has recently revealed that serines are dephosphorylated as splicing continues, indicating how far along the mRNA strand is in splicing. Dephosphorylation then serves as a signal to the cell that the mRNA is ready to be exported out of the nucleus. Rephosphorylation then appears to trigger the SR protein to enter back into the nucleus. | ||
The SR domain also appears to modulate mRNA stability, though different SR proteins have been shown to have greater effects. Some SR proteins appears to increase the sensitivity of certain mRNA sequences to degradation; this degradation appears to be controlled by SR domain interactions with the 3’ UTR of the pre-mRNA. These effects are not present without the SR domain of the protein. The destabilizing effect of SRp20 specifically has yet to be studied<ref name="Hargous">PMID:17036044</ref>. | The SR domain also appears to modulate mRNA stability, though different SR proteins have been shown to have greater effects. Some SR proteins appears to increase the sensitivity of certain mRNA sequences to degradation; this degradation appears to be controlled by SR domain interactions with the 3’ UTR of the pre-mRNA. These effects are not present without the SR domain of the protein. The destabilizing effect of SRp20 specifically has yet to be studied<ref name="Hargous">PMID:17036044</ref>. | ||
== 9G8 and SRP20 == | == 9G8 and SRP20 == | ||
[https://en.wikipedia.org/wiki/SFRS7 9G8] is another SR protein that is 80% similar in amino acid sequence. They are two of the smallest proteins in the SR family and both contain an RRM that promotes export of mRNA through interaction with the TAP protein. The only other protein shown to promote transport through the TAP protein is SF2, one of the first SR proteins discovered<ref name="Huang">PMID:12667464</ref>. Both RRMs adopt a βαββαβ mentioned earlier. Both RRMs interact with RNA with limited selectivity and therefore recognize many different RNA sequences. The 9G8 RRM contains an large hydrophobic core on its B-sheet. Observing the 9G8 protein has proved useful in understanding SRp20 less stable protein structure. In fact, the one of the only significant structural difference between the two proteins lies in the loops between a-helix 2 and B-4 where several amino acids are not conserved. | [https://en.wikipedia.org/wiki/SFRS7 9G8] is another SR protein that is 80% similar in amino acid sequence. They are two of the smallest proteins in the SR family and both contain an RRM that promotes export of mRNA through interaction with the TAP protein. The only other protein shown to promote transport through the TAP protein is SF2, one of the first SR proteins discovered<ref name="Huang">PMID:12667464</ref>. Both RRMs adopt a βαββαβ mentioned earlier. Both RRMs interact with RNA with limited selectivity and therefore recognize many different RNA sequences. The 9G8 RRM contains an large hydrophobic core on its B-sheet. Observing the 9G8 protein has proved useful in understanding SRp20 less stable protein structure. In fact, the one of the only significant structural difference between the two proteins lies in the loops between a-helix 2 and B-4 where several amino acids are not conserved. | ||
Aside from the RRM, both proteins have one SR-rich domain although 9G8 includes about 40 more amino acids this domain<ref name="Corbo2013">PMID:23685143</ref>. [[Image:9G8srp20comparison.png|300px|right|thumb|'''Figure 5.''' SRp20 and 9G8 proteins. The PDB file for SRp20 (left; PDB file: 2i2y) does not include the SR-rich domain but 9G8 (right; PDB file: 2hvz) does. Boxed image shows an RSR region in the PG8 protein with oxygens highlighted in red. Images taken from PyMol software.jpg]] Within the bigger 9G8 protein, there is a zinc knuckle that allows for binding of pyrimidine-rich RNA sequences. This zinc knuckle is not present in SRp20, lending the protein to binding of more purine-rich sequences<ref name="Huang">PMID:12667464</ref>. Not only are these two proteins similar, but they also play similar roles in mRNA export out of the nucleus. Both move continuously between the nucleus and cytoplasm which requires phosphorylation of its serine residues located in the SR-rich domain. Serine phosphorylation has been shown to have great importance in the proper functioning of many SR proteins | Aside from the RRM, both proteins have one SR-rich domain although 9G8 includes about 40 more amino acids this domain<ref name="Corbo2013">PMID:23685143</ref>. [[Image:9G8srp20comparison.png|300px|right|thumb|'''Figure 5.''' SRp20 and 9G8 proteins. The PDB file for SRp20 (left; PDB file: 2i2y) does not include the SR-rich domain but 9G8 (right; PDB file: 2hvz) does. Boxed image shows an RSR region in the PG8 protein with oxygens highlighted in red. Images taken from PyMol software.jpg]] Within the bigger 9G8 protein, there is a zinc knuckle that allows for binding of pyrimidine-rich RNA sequences. This zinc knuckle is not present in SRp20, lending the protein to binding of more purine-rich sequences<ref name="Huang">PMID:12667464</ref>. Not only are these two proteins similar, but they also play similar roles in mRNA export out of the nucleus. Both move continuously between the nucleus and cytoplasm which requires phosphorylation of its serine residues located in the SR-rich domain. Serine phosphorylation has been shown to have great importance in the proper functioning of many SR proteins<ref name="Shepard">PMID:19857271</ref>. | ||
</StructureSection> | </StructureSection> | ||
== Medical Significance == | == Medical Significance == | ||
