Structural highlights
Function
PRP2_YEAST Involved in pre-mRNA splicing. Is required together with ATP and at least one other factor, for the first cleavage-ligation reaction. Functions as a molecular motor in the activation of the precatalytic spliceosome for the first transesterification reaction of pre-mRNA splicing by hydrolyzing ATP to cause the activation of the spliceosome without the occurrence of splicing. Capable of hydrolyzing nucleoside triphosphates in the presence of single-stranded RNAs such as poly(U).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Spliceosome remodeling, executed by conserved ATPase/helicases including Prp2, enables pre-mRNA splicing. However, the structural basis for the function of the ATPase/helicases remains poorly understood. Here, we report atomic structures of Prp2 in isolation, Prp2 complexed with its coactivator Spp2, and Prp2-loaded activated spliceosome, and results of structure-guided biochemical analysis. Prp2 weakly associates with the spliceosome and cannot function without Spp2, which stably associates with Prp2 and anchors on the spliceosome, thus tethering Prp2 to the activated spliceosome and allowing Prp2 to function. Pre-mRNA is loaded into a featured channel between the N- and C-halves of Prp2, where Leu536 from the N-half and Arg844 from the C-half prevent backward sliding of pre-mRNA toward its 5'-end. ATP binding and hydrolysis trigger inter-domain movement in Prp2, which drives unidirectional step-wise translocation of pre-mRNA toward its 3'-end. These conserved mechanisms explain the coupling of spliceosome remodeling to pre-mRNA splicing.
Mechanism of spliceosome remodeling by the ATPase/helicase Prp2 and its coactivator Spp2.,Bai R, Wan R, Yan C, Jia Q, Lei J, Shi Y Science. 2020 Nov 26. pii: science.abe8863. doi: 10.1126/science.abe8863. PMID:33243853[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Edwalds-Gilbert G, Kim DH, Silverman E, Lin RJ. Definition of a spliceosome interaction domain in yeast Prp2 ATPase. RNA. 2004 Feb;10(2):210-20. PMID:14730020
- ↑ Kim SH, Smith J, Claude A, Lin RJ. The purified yeast pre-mRNA splicing factor PRP2 is an RNA-dependent NTPase. EMBO J. 1992 Jun;11(6):2319-26. PMID:1534753
- ↑ King DS, Beggs JD. Interactions of PRP2 protein with pre-mRNA splicing complexes in Saccharomyces cerevisiae. Nucleic Acids Res. 1990 Nov 25;18(22):6559-64. PMID:2251118
- ↑ Teigelkamp S, McGarvey M, Plumpton M, Beggs JD. The splicing factor PRP2, a putative RNA helicase, interacts directly with pre-mRNA. EMBO J. 1994 Feb 15;13(4):888-97. PMID:8112302
- ↑ Kim SH, Lin RJ. Spliceosome activation by PRP2 ATPase prior to the first transesterification reaction of pre-mRNA splicing. Mol Cell Biol. 1996 Dec;16(12):6810-9. PMID:8943336
- ↑ Bai R, Wan R, Yan C, Jia Q, Lei J, Shi Y. Mechanism of spliceosome remodeling by the ATPase/helicase Prp2 and its coactivator Spp2. Science. 2021 Jan 8;371(6525):eabe8863. PMID:33243853 doi:10.1126/science.abe8863
