A distinct complex of PRP19-related and trypanosomatid-specific proteins is required for pre-mRNA splicing in trypanosomes

Abstract

The pre-mRNA splicing factor PRP19 is recruited into the spliceosome after forming the PRP19/CDC5L complex in humans and the Nineteen complex in yeast. Additionally, ‘PRP19-related’ proteins enter the spliceosome individually or in pre-assemblies that differ in these systems. The protistan family Trypanosomatidae, which harbors parasites such as Trypanosoma brucei, diverged early during evolution from opisthokonts. While introns are rare in these organisms, spliced leader trans splicing is an obligatory step in mRNA maturation. So far, ∼70 proteins have been identified as homologs of human and yeast splicing factors. Moreover, few proteins of unknown function have recurrently co-purified with splicing proteins. Here we silenced the gene of one of these proteins, termed PRC5, and found it to be essential for cell viability and pre-mRNA splicing. Purification of PRC5 combined with sucrose gradient sedimentation revealed a complex of PRC5 with a second trypanosomatid-specific protein, PRC3, and PRP19-related proteins SYF1, SYF3 and ISY1, which we named PRP19-related complex (PRC). Importantly, PRC and the previously described PRP19 complex are distinct from each other because PRC, unlike PRP19, co-precipitates U4 snRNA, which indicates that PRC enters the spliceosome prior to PRP19 and uncovers a unique pre-organization of these proteins in trypanosomes.

Research Progress of DUB Enzyme in Hepatocellular Carcinoma

“…New research shows that the interaction of Prdx1 with UCH37 attenuates the effects of UCH37 on cell migration and invasion; this interaction may be through the formation of a complex rather than the deubiquitination of UCH37 itself, but the mechanism of the two on the development of liver cancer has not yet been elucidated ( 181 ). UCH37 can also act on the RNA splicing factor PRP19 through deubiquitination ( 182 ), and their interaction can promote HCC migration and invasion ( 176 ).…”

BCAS2 regulates oocyte meiotic prophase I by participating in mRNA alternative splicing

“…16 Serine and arginine rich splicing factor 3 (SRSF3) is essential for the development of fertile oocytes, as it controls the transcriptional properties of the maternal transcriptome, and heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) governs a network of alternative splicing (AS) events in germ cells via recruitment of polypyrimidine tract binding protein 2 (PTBP2) and SRSF3. 17,18 BCAS2 is one of the components of the PRP19/CDC5L complex, 19 which plays a central role in the catalytic activation of the spliceosome, 20 and PRP19 and its related proteins are major components of the spliceosome's catalytic core RNP. 19 Previous studies have reported that loss of BCAS2 in oocytes leads to poor oocyte quality, abnormal oogenesis, and disrupted follicular development.…”

“…BCAS2 is one of the components of the PRP19/CDC5L complex, 19 which plays a central role in the catalytic activation of the spliceosome, 20 and PRP19 and its related proteins are major components of the spliceosome's catalytic core RNP 19 . Previous studies have reported that loss of BCAS2 in oocytes leads to poor oocyte quality, abnormal oogenesis, and disrupted follicular development.…”