TENT enzymes introduce untemplated nucleotides to various substrates. These factors include not only the famous poly-A polymerase that generates mature 3' mRNA ends, but other enzymes with other nucleotide specificity and substrates. With my combined interests in both 3' end formation as well as miRNA biogenesis, I made the fundamental finding which reveals intron-derived hairpins and mirtrons comprise the dominant substrate for 3' tailing by multiple TENT enzymes. We provide evidence that hairpin tailing is inhibitory for ssdRNA/mirtron biogenesis and/or function, and that this pathway has restricted the evolution of canonical pre-miRNAs that resemble splicing products. Also, we show that hundreds of novel structured splicing-derived RNA (ssdRNA) hairpins are detected in intermediate RNA data, which do not yield small RNAs. We proposed that this massive contamination requires a genomic defense and we found that combination of nucleotidyltransferase enzymes specifically tail mirtrons and ssdRNAs and suppress their biogenesis and function.
Related Publications
Lee et al, Cell Reports 2023