Precursor messenger RNA splice site and splicing regulatory element

Pre-mRNA splice sites are short nucleotide sequences at exon–intron boundaries in pre-mRNA that define where the spliceosome removes introns and joins exons during RNA processing[8][6]. Splicing regulatory elements (SREs) are cis-acting sequence motifs—such as exonic and intronic enhancers and silencers (ESE/ISE/ESS/ISS)—that recruit specific RNA-binding proteins (e.g., SR proteins, hnRNPs)[1][2] and modulate alternative splicing by activating or repressing adjacent splice sites[1][5][6]. These elements are critical for controlling gene expression, enabling tissue-specific and developmental-stage-specific protein isoforms, and regulating cellular physiology[3][5]. Mutations or misregulation at these sites contribute to cancer, neurodegenerative, and many genetic diseases[5][8]. Both small-molecule and oligonucleotide drugs can therapeutically target splicing regulatory elements by correcting aberrant splicing patterns[7][8].

Other names

Splice siteSplicing regulatory element (SRE)Exonic splicing enhancer (ESE)Exonic splicing silencer (ESS)Intronic splicing enhancer (ISE)Intronic splicing silencer (ISS)Cis-acting splicing elementPre-mRNA splicing signalRNA splicing signal

Binding splice sites or SREs to block or enhance spliceosome recruitment; Masking/inhibiting silencer or enhancer sequences; Modulating RNA structure to influence splice site accessibility; Destabilizing abnormal splice junctions; Indirect alteration of splicing factor activity via small molecules[7][8]