High impact information on PRP43

• Ntr1 interacted with Prp43 through the N-terminal G-patch domain, with Ntr2 through a middle region, and with itself through the carboxyl half of the protein [1].
• The affinity-purified Ntr1-Ntr2-Prp43 complex could catalyze disassembly of the spliceosome in an ATP-dependent manner, separating U2, U5, U6, NTC (NineTeen Complex), and lariat-intron [1].
• Stringent proteomic and two-hybrid analyses show that Spp382p also interacts with Cwc23p, a DNA J-like protein present in the spliceosome and copurified with the Prp43p DExD/H-box ATPase [2].
• Prp43: An RNA helicase-like factor involved in spliceosome disassembly [3].
• Thus, the hypothesis that mDEAH9 represents the mammalian homologue of yeast Prp43 is supported by its high sequence homology, functional complementation, and colocalization with a known splicing factor in the nucleus [4].

Biological context of PRP43

• The T384A and T384V proteins were proficient for ATP hydrolysis, suggesting that ATPase activity is necessary, but not sufficient, for Prp43 function [5].
• Such Prp43 mutants exerted dominant-negative growth phenotypes when expressed in wild type cells and blocked intron release in vitro when added to yeast splicing extracts [5].
• We propose that Ntr1 promotes release of excised introns from splicing complexes by acting as a spliceosome receptor or RNA-targeting factor for Prp43, possibly assisted by the Ntr2 protein [6].
• We propose that Prp43p promotes recycling of snoRNAs and biogenesis factors during pre-rRNA processing, similar to its recycling role in pre-mRNA splicing [7].

Anatomical context of PRP43

• Prp43p could also play a role in ribosome synthesis, since it accumulates in the nucleolus [8].

Associations of PRP43 with chemical compounds

• Here, we assessed the effects of alanine and conservative substitutions at conserved residues in motifs Ia ((146)TQPRRVAA(153)), IV ((307)LLFLTG(312)), and V ((376)TNIAETSLT(384)) and thereby identified Arg150 (motif Ia), Phe309 (motif IV), Thr376, Leu383, and Thr384 (motif V) as being important for Prp43 function in vivo [5].
• Saccharomyces cerevisiae Prp43 is a DEAH-box RNA-dependent ATPase that catalyzes the release of excised lariat intron from the mRNA spliceosome [5].

Other interactions of PRP43

• Recently, mammalian homologues of Prp43p and Prp22p have been described, supporting the idea that splicing in yeast and man is phylogenetically conserved [9].
• Ntr1 interacts directly or indirectly with the intron release factor Prp43 and is required for its association with the excised intron [6].
• The known function of the DEXH/D-box protein Prp43p is the removal of the U2, U5, and U6 snRNPs from the postsplicing lariat-intron ribonucleoprotein complex [10].

Analytical, diagnostic and therapeutic context of PRP43

• Microarray analysis of pre-mRNA splicing defects in prp43 mutants shows a very mild effect, similar to that of nonessential pre-mRNA splicing factors [10].

References