User:Wally Novak/Sandbox Whitaker: Difference between revisions
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==Function== | ==Function== | ||
===General Overview=== | ===General Overview=== | ||
The U5 snRNP consists of several proteins which are highly conserved from yeast to humans. These proteins consist of Prp8, Snu114, Brr2, Prp28, Snu40/52K, and Dib1<ref>PMID:11720284</ref>, however, only Prp8, Snu114, and Brr2 remain in complex with the U5 snRNA while the spliceosome is activated <ref name="Irish">PMID:23354046</ref>. These proteins are necessary for the remodeling of the spliceosome and may play a role in maintaining catalytic activity at the active center of the spliceosome <ref name="Irish" />. Assembly of the U5 snRNP is followed by the formation of the U4/U6.U5 tri-snRNP which is the last remaining complex necessary to form the complete spliceosome and is therefore vital for its function. | The U5 snRNP consists of several proteins which are highly conserved from yeast to humans. These proteins consist of Prp8, Snu114, Brr2, Prp28, Snu40/52K, and <scene name='79/798410/Dib1/1'>Dib1</scene><ref>PMID:11720284</ref>, however, only Prp8, Snu114, and Brr2 remain in complex with the U5 snRNA while the spliceosome is activated <ref name="Irish">PMID:23354046</ref>. These proteins are necessary for the remodeling of the spliceosome and may play a role in maintaining catalytic activity at the active center of the spliceosome <ref name="Irish" />. Assembly of the U5 snRNP is followed by the formation of the U4/U6.U5 tri-snRNP which is the last remaining complex necessary to form the complete spliceosome and is therefore vital for its function. | ||
===U5 snRNA=== | ===U5 snRNA=== | ||
The U5 snRNA interacts directly with the 5’ exon before the first step of splicing and with the 5’ and 3’ exons following the first step of splicing <ref name="Keefe">PMID:9430647</ref>. These U5–exon interactions are essential for tethering and aligning the exons for ligation during the second step of splicing <ref name="Keefe" />. | The U5 snRNA interacts directly with the 5’ exon before the first step of splicing and with the 5’ and 3’ exons following the first step of splicing <ref name="Keefe">PMID:9430647</ref>. These U5–exon interactions are essential for tethering and aligning the exons for ligation during the second step of splicing <ref name="Keefe" />. | ||
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Snu114 is the only GTPase associated with the spliceosome and it has multiple contacts with Prp8 as well as U5 snRNA and Brr2 but its role in spliceosome function is not yet well-defined. <ref name="Irish" />. | Snu114 is the only GTPase associated with the spliceosome and it has multiple contacts with Prp8 as well as U5 snRNA and Brr2 but its role in spliceosome function is not yet well-defined. <ref name="Irish" />. | ||
==Structural Highlights== | ==Structural Highlights== | ||
Four sequences are highly conserved within the U5 snRNA and it is believed that these sequences play a primary role in the proteins binding capabilities. The four regions are the Stem-loop 1, Internal loop 1, Stem-closing internal loop 1, and Sm protein binding site <ref name="Frank">PMID:8114748</ref>. Stem-loop 1 spans nucleotides 84 to 110 (S. cerevisiae) and consists of a highly conserved 11 nucleotide block with complementary sequences on either side <ref name="Frank" />. These complementary sequences enable local base-pairing to form the stem of the loop <ref name="Frank" />. The U5 snRNA stem-loop 1 is necessary for tethering and aligning exons for ligation during the second step of splicing. The U5 snRNA stem 1 and internal loop 1 (IL1) are also highly conserved between yeast and humans, both in size and in structure <ref name="Frank" />. The U5 snRNA IL1 was found to be the most important region for the association of Prp8, Snu114 and Brr2 with the U5 snRNA <ref>PMID:23857713</ref>. Genetic analysis also identified the U5 snRNA IL1 as being important for Brr2 function <ref name="Frank" />. Overall, the U5 snRNA IL1 appears to be critical for the association of the U5 snRNP proteins Prp8, Snu114 and Brr2 with the U5 snRNA to form the U5 snRNP <ref name="Frank" />. | Four sequences are highly conserved within the U5 snRNA and it is believed that these sequences play a primary role in the proteins binding capabilities. The four regions are the Stem-loop 1, Internal loop 1, Stem-closing internal loop 1, and Sm protein binding site <ref name="Frank">PMID:8114748</ref>. Stem-loop 1 spans nucleotides 84 to 110 (S. cerevisiae) and consists of a highly conserved 11 nucleotide block with complementary sequences on either side <ref name="Frank" />. These complementary sequences enable local base-pairing to form the stem of the loop <ref name="Frank" />. The U5 snRNA stem-loop 1 is necessary for tethering and aligning exons for ligation during the second step of splicing. The U5 snRNA stem 1 and internal loop 1 (IL1) are also highly conserved between yeast and humans, both in size and in structure <ref name="Frank" />. The U5 snRNA IL1 was found to be the most important region for the association of Prp8, Snu114 and Brr2 with the U5 snRNA <ref>PMID:23857713</ref>. Genetic analysis also identified the U5 snRNA IL1 as being important for Brr2 function <ref name="Frank" />. Overall, the U5 snRNA IL1 appears to be critical for the association of the U5 snRNP proteins Prp8, Snu114 and Brr2 with the U5 snRNA to form the <scene name='79/798410/Prp8_snu114_brr2_5gan/2'>U5 snRNP</scene> <ref name="Frank" />. | ||
===Brr2 Structural Highlights=== | ===Brr2 Structural Highlights=== | ||
<Structure load='3hib' size='400' frame='true' align='right' caption='Brr2'/> | <Structure load='3hib' size='400' frame='true' align='right' caption='Brr2'/> | ||
