PRPF19

PSO4 is the human homolog of yeast Pso4, a gene essential for cell survival and DNA repair (Beck et al., 2008 [PubMed 18263876]).[supplied by OMIM

Full Name

PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)

Function

Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:28076346, PubMed:29360106, PubMed:29301961, PubMed:30705154).
Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity. During assembly of the spliceosome, mediates 'Lys-63'-linked polyubiquitination of the U4 spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal complex (PubMed:20595234).
Recruited to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also couple the transcriptional and spliceosomal machineries (PubMed:21536736).
The XAB2 complex, which contains PRPF19, is also involved in pre-mRNA splicing, transcription and transcription-coupled repair (PubMed:17981804).
Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L complex, plays a role in the DNA damage response/DDR. It is recruited to the sites of DNA damage by the RPA complex where PRPF19 directly ubiquitinates RPA1 and RPA2. 'Lys-63'-linked polyubiquitination of the RPA complex allows the recruitment of the ATR-ATRIP complex and the activation of ATR, a master regulator of the DNA damage response (PubMed:24332808).
May also play a role in DNA double-strand break (DSB) repair by recruiting the repair factor SETMAR to altered DNA (PubMed:18263876).
As part of the PSO4 complex may also be involved in the DNA interstrand cross-links/ICLs repair process (PubMed:16223718).
In addition, may also mediate 'Lys-48'-linked polyubiquitination of substrates and play a role in proteasomal degradation (PubMed:11435423).
May play a role in the biogenesis of lipid droplets (By similarity).
May play a role in neural differentiation possibly through its function as part of the spliceosome (By similarity).

Biological Process

DNA damage checkpoint signalingManual Assertion Based On ExperimentIMP:UniProtKB
Double-strand break repair via nonhomologous end joiningManual Assertion Based On ExperimentIMP:UniProtKB
Lipid biosynthetic processIEA:Ensembl
mRNA splicing, via spliceosomeManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of astrocyte differentiationIEA:Ensembl
Positive regulation of mRNA splicing, via spliceosomeIEA:Ensembl
Positive regulation of neuron differentiationIEA:Ensembl
Proteasomal protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Protein K63-linked ubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Protein localizationManual Assertion Based On ExperimentIMP:UniProtKB
Protein polyubiquitinationManual Assertion Based On ExperimentIDA:MGI
Spliceosomal complex assemblyManual Assertion Based On ExperimentIMP:BHF-UCL
Spliceosomal tri-snRNP complex assemblyManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Nucleus
Nucleus, nucleoplasm
Cytoplasm, cytoskeleton, spindle
Cytoplasm
Lipid droplet
Nucleoplasmic in interphase cells. Irregularly distributed in anaphase cells. In prophase cells, uniformly distributed, but not associated with condensing chromosomes. Found in extrachromosomal regions in metaphase cells. Mainly localized to the mitotic spindle apparatus when chromosomes segregate during anaphase. When nuclei reform during late telophase, uniformly distributed in daughter cells and displays no preferred association with decondensing chromatin. Recruited on damaged DNA at sites of double-strand break.