Prp24

This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada.

To get started: Click the edit this page tab at the top. Save the page after each step, then edit it again. Click the 3D button (when editing, above the wikitext box) to insert Jmol. show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page. Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc. More help: Help:Editing

Template:STRUCTURE 2ghp

Prp24 (Pre-mRNA splicing Protein 24) is a Saccharomyces cerevisiae yeast protein that functions in the formation of base pair interactions between the U6 and U4 snRNPs (small nuclear ribonucleoproteins to form the U4/U6 di-snRNP in the assembly of the spliceosome. This protein is an octamer containing four RNA recognition motifs (RRMs) that function in the binding of Prp24 to U6 snRNA. These RRMs domains are conserved in structure and sequence in proteins orthologous to Prp24 in Homo sapiens and Schizosaccharomyces pombe, as well as in other proteins containing RRMs.

IntroductionIntroduction

Pre-mRNA SplicingPre-mRNA Splicing

Pre-mRNA splicing is an essential process in eukaryotes that removes non-coding introns from a pre-mRNA transcript and splices coding exons together before the mRNA is exported from the nucleus for translation into a protein. Splicing requires five snRNPs (U1, U2, U4, U5, U6), several other proteins, and the input of energy from ATP. The U1 and U2 snRNPs assemble individually on the pre-mRNA transcript, while U4 and U6 form a U4/U6 di-snRNP before interacting with U5 to form a U4/U6.U5 tri-snRNP that interacts with U1 and U2 at the pre-mRNA transcript. U4 and U1 then depart, and after conformational changes and base pair formation with the pre-mRNA the remaining snRNPs form the catalytically active spliceosome. Two transesterification reactions then occur; the first reaction is the nucleophillic attack of the a phosphate group at the end of the 5' exon by the 2' hydroxyl of a specific adenosine at the branch point sequence of the intron. This is then followed by the nucleophillic attack of the phosphorous group linking the 3' exon to the intron by the 3' hydroxyl of the 5' exon. These splicing reactions, in addition to the addition of 7-methylguanosine 5' cap and a 3' polyadenosine tail, results in a mature mRNA transcript that can be exported from the nucleus and translated into protein.

U6 and U4 snRNPsU6 and U4 snRNPs

U6 is considered to be one of the most catalytically important snRNAs in the spliceosome, as it interacts directly with the 5' splice site through base pairing. It is thought to undergoe three conformational changes throughout the entire process of splicing and splicesome assembly; it exists as one conformation as free U6 snRNP, another conformation as part of the U4/U6 di-snRNP and a third conformation associated with U2 and the pre-mRNA. In addition to Prp24, U6 is associated with seven other proteins, Lsm 2-8, which form a ring around the 3' portion of the U6 snRNA.

The U4 snRNA is though to be non-catalytic because it leaves the spliceosome before the transesterification reactions occur. Its function is instead thought to be aiding U6 in maintaining a conformation that will enable it to interact with U2 and the 5' splice site. The U4 snRNP contains the U4 snRNA, a ring complex of the Sm proteins B-G, and the proteins Prp3, Prp4, and Snu13.

The annealing of the U4 and U6 snRNAs to form the U4/U6 di-snRNP complex, which contains the additional proteins Prp6 and Prp31, is an essential process in the formation of the spliceosome. It enables interaction with the U5 snRNP to form the U4/U6.U5 complex which serves to deliver the U5 and U6 snRNPs to the appropriate sites in the pre-spliceosome complex to form a catalytically active spliceosome upon departure of U1 and U4.

Role of Prp24 in SplicingRole of Prp24 in Splicing

Prp24 functions in the annealing of the U4 and U6 snRNPs of the assembling spliceosome.

StructureStructure

spinqualitylabelsall models NMR structure of RRM1 and RRM2 of Prp24 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Functional InteractionsFunctional Interactions

Lsm ProteinsLsm Proteins

spinqualitylabelsall models NMR structure of RRM2 of Prp24 bound to a portion of U6 snRNA Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image