Secondary structure of pre-mRNA introns for genes in the 15q11-12 locus. Mapping of functionally significant motives for RNA-binding proteins and nucleosome positioning signals

Abstract

AbstractIn this study, we identified reproducible substructures in the folded structures of long intron RNAs for recursive spliced variants and annotated pre-mRNA for GABRB3 and GABRA5. We mapped the RNA motives recognized by RNA-binding proteins for the specified locus and characterized the area of preferred localization. A comparison of pre-mRNA variants revealed the dominant type of protein potential effects. We determined the structural specifics of RNA in the dense Alu cluster and clarified the analogy of apical substructure to the A-Xist fragment of transcriptional variant. Mapping of the nucleosome potential reveals alternation of strong and weak signals at the 3’-end portion of GABRB3 and clusters of nucleosome positioning signal in the vicinity of the Alu cluster. Distribution of simple oligonucleotides among reproducible substructures revealed an enrichment in Py-tracts; for some of them, this may be considered as a complementary supplement to the Pu-tract enrichment of ncRNA Malat1 as a component of nuclear speckles. The secondary structure elements of bidirectional transcripts are predisposed for somatic homolog pairing in this locus, as was previously shown experimentally.A model of potential intron RNA influence on splicing has been suggested based on its interaction with Py-tract-binding RNP, serine-arginine SRSF proteins, ncRNA Malat1, as well as the action of Alu cluster.