User:Guilherme Gonzalez/Sandbox 1
From Proteopedia
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HSH155<sup>HEAT</sup> is a core splicing factor that is associated with the U2 small nuclear ribonucleoproteins complex (U2 snRNA), a component of the spliceosome of ''Saccharomyces cerevisiae''. The HSH155 is a major component to the splicing of the pre-mRNA, this protein binds with the pre-mRNA upstream of the intron branching site no matter the sequence of this RNA, anchoring the U2 snRNA to the pre-mRNA. | HSH155<sup>HEAT</sup> is a core splicing factor that is associated with the U2 small nuclear ribonucleoproteins complex (U2 snRNA), a component of the spliceosome of ''Saccharomyces cerevisiae''. The HSH155 is a major component to the splicing of the pre-mRNA, this protein binds with the pre-mRNA upstream of the intron branching site no matter the sequence of this RNA, anchoring the U2 snRNA to the pre-mRNA. | ||
| - | The HSH155 is composed by a single peptide, the structure of the region closer to the N-terminal is still unresolved but the rest of this protein is composed by a series of alpha helices in tandem, denominated HEAT repeat, this structure is characterized by repetitions of two alpha helices linked by a short loop, forming a solenoid form that resembles the letter “C” <ref>DOI 10.2210/pdb7OQB/pdb< | + | The HSH155 is composed by a single peptide, the structure of the region closer to the N-terminal is still unresolved but the rest of this protein is composed by a series of alpha helices in tandem, denominated HEAT repeat, this structure is characterized by repetitions of two alpha helices linked by a short loop, forming a solenoid form that resembles the letter “C” <ref>DOI 10.2210/pdb7OQB/pdb</ref>. |
This structure is essential to the function of this protein, allowing ligants to interact with the innermost part of this molecule and alter its opening, being capable of small regulations in its capacity to interact with the pre-RNAm and other molecules of the U2 snRNA. Besides that, this structure has two main states: Open and Closed<ref>DOI 10.1038/s41586-021-03789-5</ref>. This can be regulated and permits the interaction and the fixation of the pre-RNAm, and this process allows the formation of the A complex during the splicing. | This structure is essential to the function of this protein, allowing ligants to interact with the innermost part of this molecule and alter its opening, being capable of small regulations in its capacity to interact with the pre-RNAm and other molecules of the U2 snRNA. Besides that, this structure has two main states: Open and Closed<ref>DOI 10.1038/s41586-021-03789-5</ref>. This can be regulated and permits the interaction and the fixation of the pre-RNAm, and this process allows the formation of the A complex during the splicing. | ||
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== U2 snRNA == | == U2 snRNA == | ||
| - | The HSH155<sup>HEAT</sup> is a major component of the <scene name='89/897726/Allfilled/1'>U2 snRNA complex</scene>, this complex is present in almost all of the eukaryotes already studied<ref>DOI 10.1038/s41422-018-0094-7< | + | The HSH155<sup>HEAT</sup> is a major component of the <scene name='89/897726/Allfilled/1'>U2 snRNA complex</scene>, this complex is present in almost all of the eukaryotes already studied<ref>DOI 10.1038/s41422-018-0094-7</ref>. This means that similar components like the HSH155<sup>HEAT</sup> are also present. In humans this protein is the SF3B1 (Splicing factor 3B subunit 1). Both have similar structure and the presence of the HEAT repeats on the C terminal part of the protein. |
| - | In eukaryotes the U2 snRNA is essential for the assembly of the Pre-A complex, because of the ability to recognize and bind to the intron on mRNA primary transcripts. This highly dependent on the HSH155<sup>HEAT</sup>, but the U2 snRNA also has been proposed to have a catalytic purpose on the splicing. Although this function is not a direct result of the interaction of the RNAm with the HSH155<sup>HEAT</sup>, this protein is also involved by regulating the attachment and the movement of associated proteins in this complex when it shifts between the open and close states<ref>DOI 10.1101%2Fgad.253708.114< | + | In eukaryotes the U2 snRNA is essential for the assembly of the Pre-A complex, because of the ability to recognize and bind to the intron on mRNA primary transcripts. This highly dependent on the HSH155<sup>HEAT</sup>, but the U2 snRNA also has been proposed to have a catalytic purpose on the splicing. Although this function is not a direct result of the interaction of the RNAm with the HSH155<sup>HEAT</sup>, this protein is also involved by regulating the attachment and the movement of associated proteins in this complex when it shifts between the open and close states<ref>DOI 10.1101%2Fgad.253708.114</ref>. |
The U2 snRNA can vary vastly between all eukaryotes, having different lengths and sequences according to the species. But that is also some very conservated parts of this complex and the HEAT repeats are one of them. This fact indicates how important this protein and this component are to the process of splicing. | The U2 snRNA can vary vastly between all eukaryotes, having different lengths and sequences according to the species. But that is also some very conservated parts of this complex and the HEAT repeats are one of them. This fact indicates how important this protein and this component are to the process of splicing. | ||
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== Diseases == | == Diseases == | ||
| - | In humans, mutations in the SF3B1 protein are linked to some diseases like myelodysplastic syndrome, breast cancer and chronic lymphocytic leukemia. In a recent study 9.7% of patients with chronic lymphocytic leukemia had mutations in the SF3B1, and although mutations in this protein don’t account for all of the cases of these conditions, they are also linked with an increased progression rate and severity in these patients<ref>DOI 10.1182/blood-2011-09-377275< | + | In humans, mutations in the SF3B1 protein are linked to some diseases like myelodysplastic syndrome, breast cancer and chronic lymphocytic leukemia. In a recent study 9.7% of patients with chronic lymphocytic leukemia had mutations in the SF3B1, and although mutations in this protein don’t account for all of the cases of these conditions, they are also linked with an increased progression rate and severity in these patients<ref>DOI 10.1182/blood-2011-09-377275</ref>. |
Revision as of 00:54, 6 December 2021
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References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
- ↑ doi: https://dx.doi.org/10.2210/pdb7OQB/pdb
- ↑ Zhang Z, Rigo N, Dybkov O, Fourmann JB, Will CL, Kumar V, Urlaub H, Stark H, Luhrmann R. Structural insights into how Prp5 proofreads the pre-mRNA branch site. Nature. 2021 Aug;596(7871):296-300. doi: 10.1038/s41586-021-03789-5. Epub 2021, Aug 4. PMID:34349264 doi:http://dx.doi.org/10.1038/s41586-021-03789-5
- ↑ Zhan X, Yan C, Zhang X, Lei J, Shi Y. Structures of the human pre-catalytic spliceosome and its precursor spliceosome. Cell Res. 2018 Oct 12. pii: 10.1038/s41422-018-0094-7. doi:, 10.1038/s41422-018-0094-7. PMID:30315277 doi:http://dx.doi.org/10.1038/s41422-018-0094-7
- ↑ Unknown PubmedID 10.1101%2Fgad.253708.114
- ↑ Malcovati L, Papaemmanuil E, Bowen DT, Boultwood J, Della Porta MG, Pascutto C, Travaglino E, Groves MJ, Godfrey AL, Ambaglio I, Galli A, Da Via MC, Conte S, Tauro S, Keenan N, Hyslop A, Hinton J, Mudie LJ, Wainscoat JS, Futreal PA, Stratton MR, Campbell PJ, Hellstrom-Lindberg E, Cazzola M. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood. 2011 Dec 8;118(24):6239-46. doi: 10.1182/blood-2011-09-377275. Epub 2011, Oct 12. PMID:21998214 doi:http://dx.doi.org/10.1182/blood-2011-09-377275
