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Erring on the Side of Calling: Sequencing Mismatches Highlight RNA Editing

July 1, 2009 To err is enzymatic; to identify errors previously thought to be technical, but are actually biologically relevant, is divine. Most researchers view the sequencing errors from reverse transcription, sequencing reaction, or base calling part of the job. After all, with the mountains of sequence pouring off these platforms, one would expect and accept a few errors here and there.  A Canadian team of researchers recently showed that many of the mismatch, non-conformist sequences that are typically thrown aside during analysis, are central players in another emerging area of RNA regulation.

The team looked at a two discarded small RNA sequencing datasets containing a bunch of sequences that didn’t match up to the plant and rice reference genomes studied. They identified a few post-transcriptional modifications in the small RNA populations including miRNA. A couple of the mods that stuck out were:

• 3’ miRNA Uridylation: Although the role of 3’ uracil modification is a bit of a mystery, previous works suggested this modification might be involved in miRNA turnover, as a degradation signal.
• 5’ miRNA Deletion/ 3’ Uridylation Combo:The team uncovered some species of miRNA that were tweaked at both ends.  This 1-2 punch can impact with which AGO complex the RNAs associate.

One of the most interesting examples was miR822 which normally associates with AGO1 in the cytoplasm. The modified sibling with the 5' deletion and 3' U additions, opts to associate with the nucleolar AGO4 complex that is involved in silencing chromosomal DNA.

Check out all the details at Nucleic Acids Research May, 2009