Circular transcripts of the testis-determining gene Sry in adult mouse testis

Abstract

Sry is expressed at higher levels in the adult testis, where no function has been determined, than in the genital ridge, its critical site of action. cDNA and 5' RACE clones isolated from testis or from Sry-transfected cell lines have an unusual structure, with 3' sequences located in a 5' position. RNAase protection assays and reverse transcription polymerase chain reactions confirmed that these unusual RNA molecules represent the most abundant transcript in testis. Furthermore, oligonucleotide hybridization and RNAase H digestion proved that these Sry RNA molecules are circular. Similar transcripts were detected in the testes of mice with Mus musculus musculus, Mus musculus domesticus, and Mus spretus Sry genes. The circular RNA is found in the cytoplasm but is not substantially bound to polysomes. We suggest that the circles arise from normal splicing processes as a consequence of the unusual genomic structure surrounding the Sry locus in the mouse.

Does the linear Sry transcript function as a ceRNA for miR-138? The sense of antisense

“…Although it seems obvious that sponges are antisense to the miRNA they bind to, it should not be assumed that all circRNAs are transcripts in an antisense orientation to a protein coding gene, as occurs with CDR1as . A special feature of the Sry gene is that it can generate linear as well as circular transcripts depending on the use of alternative promoters (proximal vs distal) 8 . Capel et al reported for the first time that the circular Sry RNA is derived from a sense sequence that consists of a single exon.…”

“…This molecule is formed by the processing of a longer precursor transcript that contains one inverted repeat at each end. This unusual configuration promotes the formation of a stem-loop structure that facilitates the nucleophilic attack of a donor splicing site at the 3′ end to an acceptor site at the 5′ end, which results in its circularization 8 ( Figure 1). Thus, it can be asserted that this is, in fact, a circular sense Sry mRNA.…”

“…The newly formed 3′-OH at the SD, attacks the 5′-P at the splice acceptor (SA) site, resulting in excision of the intron and ligation of the circular exon of 1231 nucleotides. Modified from Capel et al 8 .…”

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]).…”