Multifaceted Regulation of Gene Expression by the Apoptosis- and Splicing-Associated Protein Complex and Its Components

Abstract

The differential deposition of RNA-binding proteins (RBPs) on pre-mRNA mediates the processes of gene expression. One of the complexes containing RBPs that play a crucial part in RNA metabolism is the apoptosis-and splicing-associated protein (ASAP) complex. In this review, we present a summary of the structure of ASAP complex and its localization. Also, we discuss the findings by different groups on various functions of the subunits of the ASAP complex in RNA metabolism. The subunits of the ASAP complex are RNPS1, Acinus and SAP18. Originally, the ASAP complex was thought to link RNA processing with apoptosis. Further studies have shown the role of these components in RNA metabolism of cells, including transcription, splicing, translation and nonsense-mediated mRNA decay (NMD). In transcription, RNPS1 is involved in preventing the formation of R-loop, while Acinus and SAP18 suppress transcription with the help of histone deacetylase. On the one hand, individual components of the ASAP complex, namely RNPS1 and Acinus act as splicing activators, whereas on the other hand, in-vitro assay shows that the ASAP complex behaves as splicing repressor. In addition, the individual members of the ASAP complex associates with the exon junction complex (EJC) to play roles in splicing and translation. RNPS1 increases the translation efficiency by participating in the 3'end processing and polysome association of mRNAs. Similarly, during NMD RNPS1 aids in the recruitment of decay factors by interacting with EJC.

Quantitative Proteomics Reveals a Role for SERINE/ARGININE-Rich 45 in Regulating RNA Metabolism and Modulating Transcriptional Suppression via the ASAP Complex in Arabidopsis thaliana

“…In our study, all core proteins of a conserved ASAP complex, SR45, SAP18, and ACINUS, exhibited a significantly lower level of accumulation in the sr45-1 mutant. Their orthology to the ASAP complex proteins in animal models, shown here through amino acid sequence homology and predicted protein domain structures ( Supplemental Figures S2 and S3 ), supports the hypothesis that SR45 not only functions as a splicing regulator to affect pre-mRNA splicing, but can influence transcriptional control via associations with other proteins that are not splicing factors (Song and Galbraith, 2006; Hill et al, 2008; Zhang and Mount, 2009; Day et al, 2012; Xing et al, 2015; Questa et al, 2016; Deka and Singh, 2017; Zhang et al, 2017). Such an example is its interaction with SAP18 in the ASAP complex.…”

“…SR45, an RNA-binding protein, is orthologous to RNPS1 in humans and other animals (Zhang and Mount, 2009). RNPS1 is a component of the apoptosis and splicing-associated protein (ASAP) complex (Schwerk et al, 2003), which functions to regulate RNA metabolism at multiple levels (Deka and Singh, 2017). The two other core proteins in the ASAP complex are SAP18 and ACINUS (Schwerk et al, 2003).…”

The SRSF3-MBNL1-Acin1 circuit constitutes an emerging axis to lessen DNA fragmentation in colorectal cancer via an alternative splicing mechanism

“…Acin1-L, Acin1-S , and Acin1-S' transcripts are transcribed from the Acin1 gene through alternative promoter usage or an AS mechanism [46] . All Acin1 isoforms share an RNA recognition motif, RSB domain, and RS-rich region within its C-terminus, whereas the N-terminal SAP motif within Acin1-L mediates its interaction with AT-rich DNA regions [47 , 48] . Proteomic assays indicated the nuclear distribution of the Acin1-S and Acin1-S ' isoforms, whereas the nuclear-cytoplasmic localization of the Acin1-L isoform was relevant to its SAP motif [47] .…”

Arabidopsis ACINUS is O-glycosylated and regulates transcription and alternative splicing of regulators of reproductive transitions

“…Studies in animals have identified Acinus and Pinin as essential cellular components that bridge chromatin remodeling, transcription and splicing through the formation of analogous ASAP and PSAP complexes 14,16,17,48–51 . Sequence alignment and phylogenetic analysis show that the Arabidopsis orthologs, AtACINUS and AtPININ, share higher levels of sequence similarity to their animal counterparts than to each other and appear to have evolved independently since the separation of the plant and metazoan kingdoms 14 .…”

“…Another RSB-containing protein, Pinin, forms a similar protein complex named PSAP, which has distinct biological functions 14,15 . The ASAP and PSAP complexes are believed to function at the interface between histone modification, transcription, and alternative splicing (AS) in metazoans 14,16,17 . In Arabidopsis , AtRNPS1, also known as ARGININE/SERINE-RICH 45 (SR45), has been implicated in splicing, transcription and RNA-dependent DNA methylation, with effects on multiple aspects of plant development as well as stress and immune responses 18–23 .…”