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Transcript of CircRNA
that Shocks The World Nature, Feb. 2013
2013.6.3 Natural RNA: Line or Circle?
Why we hardly ever
find them before? Hey, we're alive! ...The Story of Sponge (Bob?) Zebrafish without Sponge Bob How do they act? Infinite Possibility... Mature messenger RNAs are linear molecules with 5' and 3' termini that reflect start and stop of the RNA polymerase on the DNA template.
In cells, different RNA molecules are sometimes joined together by splicing reactions (trans-splicing), but covalent linkage of the ends of a single RNA molecule to form a circular RNA (circRNA) is usually considered a rare event. "we screened RNA-seq data for circRNAs. Compared to previous approaches our computational pipeline can find circRNAs in any genomic region, takes advantage of long (,100 nucleotides) reads, and predicts the acceptor and donor splice sites used to link the ends of the RNAs.
We do not rely on paired-end sequencing data or known splice sites. Using published 10,25,26 and our own sequencing data, our method reported thousands of circRNAs in human and mouse tissues as well as in different developmental stages of Caenorhabditis elegans." circRNA sequences were significantly enriched in conserved nucleotides, indicating that circRNAs compete with other RNAs for binding by RNA binding proteins (RBPs) or miRNAs.
Together, our data provide evidence that circRNAs form an important class of post-transcriptional regulators. "We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain.Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner." MicroRNA sponges are competitive inhibitors that are transcripts expressed from strong promoters, containing multiple, tandem binding sites to a microRNA of interest.
So a single sponge can be used to block an entire microRNA seed family and result in a loss of miRNA function. "We injected morpholinos to knock down mature miR-7 expression in zebrafish embryos. At a dose of 9 ng of miR-7 morpholino, the embryos did not show overall morphological defects but reproducibly, and in two independent genetic backgrounds, developed brain defects. In particular, 70% showed a consistent and clear reduction in midbrain size, and an additional ,5% of animals had almost completely lost their midbrains." Nothing is impossible.
Perhaps the best known circRNA is antisense to the mRNA transcribed
from the SRY (sex-determining region Y) locus and is highly expressed
in testes. ...And the result is.......
Numerous circRNAs appear to be specifically expressed across tissues or developmental stages. We validated these data and showed that most tested circRNAs are well expressed, stable and circularized using the predicted splice sites. We're not playing hide &seek! ...like sponge or
Sponge Bob Square Pants? What else can RNA look like? To be continued... Maybe...A Mobius Strip?