As deep sequencing platforms displace Nintendo’s Wii as the most popular toy in the research community, labs are discovering new varieties of RNAs at a dizzying pace. The latest edition, transcription initiation RNAs (tiRNAs), were recently identified by scientists at the University of Queensland in Australia, and published in Nature Genetics last April, by mining sequencing data that would usually be disregarded as degradation products…similar to another paper we’ve recently featured, “Erring On The Side Of Calling.”
“I think this was a situation where “chance favored the prepared mind”. The FANTOM4 data, which was at the core of our analysis, contains millions of human small RNA deep sequencing reads ranging from 10 to 100 nucleotides (nt) in size. We therefore had a unique opportunity to look at RNA species that otherwise would have been missed because deep sequencing protocols generally only focus on RNAs larger than ~20 nt, or discarded because of the assumption that smaller classes did not exist, “ explained Ryan Taft, a grad student in the Mattick Lab and key contributor to the recent work identifying tiRNAs.
Here’s where we would normally say something about how one researcher’s junk is another’s gold, or you CAN find gold in a garbage heap, but we won’t because that’s a little played out now. We see new evidence like this weekly, supporting that it’s an RNA World and tiRNAs are yet another member of it’s diverse community.
Unlike some of the larger non-coding RNAs featured recently, tiRNAs are the featherweights of the trancriptome, with most measuring about 18 nt. Although much remains to be learned about their function, there is some evidence implicating them in the transcriptional lambada:
- They originate from just downstream of transcription start sites (TSS)
- tiRNAs are associated with RNA Pol II binding
- Abundance seems to be enriched by highly expressed transcripts.
In their most recent paper in Cell Cycle, the team goes on to propose a model for the biogenesis and function of tiRNAs, suggesting that tiRNAs are formed when RNA Pol II is forced to backtrack after hitting the first nucleosome from the TSS.
So, once conceived, what do tiRNAs do? Good question. They may be nothing more than a by-product of transcription, but when you consider the recent evidence highlighting the mingling between ncRNAs and chromatin, we’d be willing to wager this group is functional.
So would Taft. “There is increasing evidence that antisense non-coding RNAs are tethered to promoter regions and recruit chromatin modifying factors. Our collaborator Kevin Morris (Scripps Institute, San Diego) has suggested that these RNAs are a constitutive epigenetic “off switch” which inhibit transcription. Our favored hypothesis is that tiRNAs might be a mechanism to target these transcripts and “turn off the off switch”.
See for yourself at Cell Cycle, August 2009 and let us know what you think.