Scrambled exons

Abstract

Using a sensitive assay for RNA expression, we identified several abnormally spliced transcripts in which exons from a candidate tumor suppressor gene (DCC) were scrambled during the splicing process in vivo. Cloning and sequencing of PCR-amplified segments of the abnormally spliced transcripts showed that exons were joined accurately at consensus splice sites, but in an order different from that present in the primary transcript. Four scrambled transcripts were identified, each involving a different pair of exons. The scrambled transcripts were found at relatively low levels in a variety of normal and neoplastic cells of rodent and human origin, primarily in the nonpolyadenylated component of cytoplasmic RNA. These results demonstrate that the splicing process does not always pair sequential exons in the order predicted from their positions in genomic DNA, thus creating a novel type of RNA product.

Splicing with inverted order of exons occurs proximal to large introns

“…The RNase-resistant products were analysed by gel electrophoresis. Protected (Nigro et al, 1991) and the authors also demonstrated that these products are not polyadenylated. Both results clearly establish that scrambling of exons may occur during the splicing process in vivo.…”

“…Aberrant annealing of homologous sequences or fortuitous protein interactions within introns leading to a particular secondary structure of the pre-mRNA, might facilitate illegitimate interactions of snRNPs to incorrectly paired exons. A possible mechanism for intramolecular splicing generating abnormally spliced product has been proposed (Nigro et al, 1991) which would generate circular RNAs, but an intermolecular reaction is also possible. Trans-splicing mechanisms described in lower eukaryotes (Agabian, 1990) bear no comparison to the scrambled splicing observed here.…”

“…In this paper we present evidence from PCR and RNase (Nigro et al, 1991). It is noteworthy that abnormal splicing occurs only with ETS-l exons c, d…”

Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway

“…1 Additional studies reported further new examples of circRNAs over the years, [2][3][4][5][6][7][8][9] yet the extent of the prevalence of the circularization phenomenon was not clear, as the available examples remained limited. The advent of high-throughput sequencing revealed that circRNAs are a large class of abundant RNAs with complex developmental-and cellspecific expression patterns.…”

Circular RNAs

“…v Although isolated examples of circularized RNA molecules were already described more than 20 years ago [1,2], it was not until quite recently that the prevalence of circular RNAs (circRNAs) was revealed. The advent of massively parallel sequencing technology allowed researchers to catalogue circRNAs across eukaryotic and prokaryotic systems (e.g., [3][4][5][6][7]).…”