Abstract
DNA ligases catalyze bond formation in the backbone of nucleic acids via
the formation of a phosphodiester bond between adjacent 5’ phosphates
and 3’ hydroxyl groups on one strand of the duplex. While DNA ligases
preferentially ligate single breaks in double stranded DNA (dsDNA), they
are capable of ligating a multitude of other nucleic acids substrates
like blunt-ended dsDNA, TA overhangs, short overhangs and various
DNA-RNA hybrids. Here we report a novel DNA ligase from Chronobacter
phage CR 9 (AZ R2D Ligase) with an unexpected DNA-to-RNA ligation
activity. The R2D ligase shows excellent efficiency when ligating DNA to
either end of RNA molecules using a DNA template. Furthermore, we show
that DNA can be ligated simultaneously to both the 5’ and 3’ ends of
microRNA-like molecules in a single reaction mixture. Abortive
adenylated side product formation is suppressed at lower ATP
concentrations and the ligase reaction reaches near completion when
ligating RNA to DNA or DNA to RNA. The ligation of a DNA strand to the
5’-PO4 end of RNA is unique among the commercially available ligases and
may facilitate novel workflows in microRNA analysis, RNA sequencing and
in the preparation of chimeric guide DNA-RNA for gene editing
applications.