SpliceAid-F: a database of human splicing factors and their RNA binding sites

Abstract

MotivationsThe pre-mRNA sequences of eukaryotes harbour multiple information layers in addition to the one specifying the aminoacid sequence. Indeed, specific signals regulating the splicing process, RNA folding, capping, polyadenylation, stability and nuclear export, overlap each other and with the coding information. Mutagenesis experiments have highlighted that splicing regulatory elements are scattered in the entire pre-mRNA sequence and that all nucleotide positions are potentially involved in the generation of the specific splicing pattern through the specific interaction with trans-acting RNA-binding proteins. In particular, the identification of cis-regulatory motifs in exonic regions, such as exonic splicing enhancers (ESEs) or silencers (ESSs), superimposed on the coding sequence of the gene can be driven by the observation of purifying selection occurring at synonymous codons [5]. The coordinated binding of combinations of regulatory proteins to their binding sites modulate the expression of specific transcript isoforms in a cell/tissue type-, development stage-, disease-and/or other condition-specific manners and may also promote or repress the formation of the spliceosome, the large (~60S) RNA-protein machinery that catalyzes intron removal. A growing list of mammalian protein factors involved in splicing regulation and their target sites in the pre-mRNA has been reported in the literature [2]. In order to establish a curated and retrievable repository of splicing regulatory factors and target sites for human genes we have recently created SpliceAid [4] that can also be used to find putative regulatory motifs in user submitted sequences. As a further evolution of SpliceAid, we present here SpliceAid-F, a database compilation of splicing regulatory factors and their experimentally validated target RNAs extracted from an exhaustive hand-curated literature search.

The emerging role of alternative splicing in senescence and aging

“…Many RNA binding proteins act as splicing regulators to facilitate or inhibit splice site recognition by spliceosome components (Fu & Ares, ). Splicing regulators include, but are not limited to, members of the hnRNP and SR families of proteins (Busch & Hertel, ; Giulietti et al ., ). The combinatorial cooperation or antagonism between distinct RNA binding proteins is thought to play a major role in conferring specificity to splicing decisions (Fu & Ares, ).…”

Mutation update for theNR5A1gene involved in DSD and infertility

“…During 46,XY embryo development, it is first expressed in the urogenital ridge and drives testicular differentiation along with the expression of SRY, SOX9 , and GATA4 genes (Hatano, Takakusu, Nomura, & Morohashi, ; Sekido & Lovell‐Badge, ). Its expression persists in the developing testis; in Sertoli cells, this transcription factor regulates the expression of AMH gene, leading to the regression of Müllerian structures, and also interacts with DHH , which is required for the development of both fetal and adult Leydig cells (Giulietti et al, ; Karpova et al, ); in Leydig cells, NR5A1 regulates the synthesis of a number of steroidogenic enzymes required for testosterone production, including StAR, leading to the virilization of external genitalia and initiating testicular descent (Parker, ; Zimmermann, Schwärzler, Buth, Engel, & Adham, ).…”

Systematic profiling of alternative splicing signature reveals prognostic predictor for prostate cancer

“…A list of 67 human splicing factors was created through hand‐planned literature and database screening 17 . The expression of the splicing factor gene in the mRNA splicing pathway was derived from level 3 mRNA‐seq data in TCGA.…”