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A new processing pathway for non-coding RNA

All life on earth follows the central dogma of biology: DNA to RNA to protein. DNA stores the genetic information and is transcribed into RNA that carries the information to the machinery used to create proteins. RNA is translated to the various amino acid sequences that fold into a variety of proteins and enzymes in the cell.

This protein-coding RNA, known as messenger RNA (mRNA), goes through a multi-step process to generate a mature functional mRNA. These mRNA molecules receive a protective structure made up of repeated adenosines called a poly(A) tail to protect the RNA from being degraded and also signal that the RNA encodes for a protein. mRNAs also goes through a process known as splicing where unnecessary RNA sequences, known as introns, are removed. After removal of the internal intron, the two neighboring mRNA fragments are joined together to form a single continuous mRNA ready for protein synthesis. This contrasts with another subset of RNA, called non-coding RNA that is not used to create proteins.

 Non-coding RNAs play many important roles in the cell and have been implicated in human disease. Some non-coding RNAs are functional and act directly on other molecules in the cell, while others regulate gene expression or act as transport molecules. Telomerase contains an essential non-coding RNA subunit and is a potential target for anti-aging and cancer therapies.

 Recently the Chen group discovered a novel mechanism that processes the telomerase RNA precursor into its mature form. This mechanism is highly conserved in filamentous fungi and distinct from the mechanism employed in vertebrates and other eukaryotes. The fungal telomerase RNA precursor initially contains an intron and a poly(A) tail. By hijacking the machinery used to remove mRNA introns and blocking the joining of the two RNA fragments by simply changing the first residue of the intron from G to A, fungal telomerase RNA is cleaved to make the mature RNA. This unique half-splicing reaction thus generates two fragments of RNA, the mature telomerase RNA, used by the telomerase enzyme, and a second fragment that is degraded. As Chen says, "It's amazing how nature continues to surprise us by grabbing bits and pieces from other systems to make a new method for RNA processing." Splicing has been studied for decades and this is the first time that this type of reaction has been found in nature and requires only a single-residue alteration in the 5' splice site of the intron.

Non-coding RNA is emerging as an important player in cellular systems and by finding a novel RNA processing pathway, we may be able to identify new classes of RNA that utilize a similar method for RNA maturation.

The work was been published this month in Nature Communications (Qi, X., D.R. Rand, J.D. Podlevsky, Y. Li, A. Mosig, P.F. Stadler and J.J.-L. Chen, Prevalent and distinct spliceosomal 3'-end processing mechanisms for fungal telomerase RNA. Nature Communications 6:6105, doi:10.1038/ncomms7105).

"Prevalent and distinct spliceosomal 3'-end processing mechanisms for fungal telomerase RNA", Xiaodong Qi, Dustin P. Rand, Joshua D. Podlevsky, Yang Li, Axel Mosig, Peter F. Stadler & Julian J. -L. Chen, Nature Communications 6, Article number: 6105, doi:10.1038/ncomms7105, Published 19 January 2015

 

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