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4 March 2013 No Comment

Mysterious world of RNAs: CIRCULAR RNAs Regulating MicroRNAs

The world of RNAs does not seems to stop surprising us, latest being CIRCULAR RNAs controlling gene expression. In past few decades we have come across many non traditional RNAs. While some were very short and some surprisingly long and some influenced gene expression by blocking other RNAs from being translated into protein. However one thing which was common to all RNAs was their linear form. Few circular RNAs were reported in plants and animals but they were dismissed as genetic errors or experimental artefacts.

In two recently published articles in Nature journal describe new form of highly stable circular RNAs act as molecular ‘sponges’, by binding to and block¬ing tiny gene modulators called microRNAs.

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. The discovery of circular RNAs once again proves that there is much more to RNA than a simple messenger between DNA and the proteins it encodes.

In a bid to study circRNAs Systematically, Nikolaus Rajewsky group sequenced and computationally analysed human, mouse and nematode RNA and detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression..

The work also clearly shows that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA ‘miR-7’.

To functionally validate CDR1as, authors expressed human CDR1as in Zebrafish embryos showed disruption of midbrain development, a phenotype reproduced by loss of mir-7, suggesting that CDR1as is a miRNA antagonist.

References:

1. Circular RNAs are a large class of animal RNAs with regulatory potency.

Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N.
Nature. 2013 Feb 27. doi: 10.1038/nature11928

2. Natural RNA circles function as efficient microRNA sponges.

Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J.
Nature. 2013 Feb 27. doi: 10.1038/nature11993
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