High impact information on PRPF19

• During catalytic activation of the spliceosome, snRNP remodeling events occur, leading to the formation of a 35S U5 snRNP that contains a large group of proteins, including Prp19 and CDC5, not found in 20S U5 snRNPs [1].
• Role of human Pso4 in mammalian DNA repair and association with terminal deoxynucleotidyl transferase [2].
• Loss of hPso4 expression induced by siRNA results in accumulation of DSBs, apoptosis, and decreased cell survival after DNA damage [2].
• A conservative Val-->Ile point mutation in the Prp19p U-box domain leads to pre-mRNA splicing defects in vivo [3].
• Mutagenesis of residues at this interface, while not perturbing the structure of the U-box, abrogates Prp19p function in vivo [4].
• Knock-out mice deficient in SNEV (hPRP19/hPSO4) are early embryonic lethal [5]
• SNEV (hPRP19/hPSO4) prolongs the replicative life span of endothelial cells upon overexpression [6].

Biological context of PRPF19

• The Pso4 mRNA splicing and DNA repair complex interacts with WRN for processing of DNA interstrand cross-links [7].
• In interphase cells, green fluorescent protein-tagged hNMP 200 was predominantly nucleoplasmic [8].
• During cell division hNMP 200 became irregularly distributed in prophase, sparing regions of condensing chromatin [8].
• SNEV (hPRP19/hPSO4) is the orthologue of the yeast splicing factor Prp19 [9]. Interfering with self assembly of SNEV (hPRP19/hPSO4) inhibits in vitro splicing as well as spliceosome assembly [4].
• Importantly, a consistent set of abundant NM proteins, some (e.g. hNMP 200) of which displaying structural features, remained unaffected during apoptosis and might therefore represent constituents of an elementary scaffold [10].
• SNEV (hPRP19/hPSO4) is a ubiquitin E3 ligase and [11] interacts directly with the proteasome [12].
• SNEV (hPRP19/hPSO4) heterozygous deletion impairs hematopoietic progenitor cell function [13]

Anatomical context of PRPF19

• hNMP 200: a novel human common nuclear matrix protein combining structural and regulatory functions [8].

Other interactions of PRPF19

• However, the hNMP 200 primary sequence contained five consensus WD-repeat sequences, indicative of participation and regulatory function in larger protein assemblies [8].
• In situ hybridizations reveal that centrin, cyclin B, and beta-tubulin mRNAs are present in both sterile and spermatogenous cells, but that transcripts encoding RNA helicase and PRP-19 (a spliceosome component) become localized in spermatogenous cells [14].
• SNEV (hPRP19/hPSO4) interacts with the novel pre-mRNA splicing factor Blom7 [15]

Analytical, diagnostic and therapeutic context of PRPF19

• Northern blot analysis and 2D protein electrophoresis showed ubiquitous expression of hNMP 200 in a variety of cell types [8].
• Sequence alignments show hNMP 200-related proteins in metazoans, plants, and yeast, the homologous Saccharomyces cerevisiae protein prp19 being an accessory, but essential, factor for pre-mRNA processing [8].
• A high-resolution structure of the homodimeric state of the Prp19 U-box was determined by X-ray crystallography [16].
• SNEV (hPRP19/hPSO4) levels are a predictor of survival in breast cancer [6].

References