SLFN-generated 3′-truncated tRNA Leu or tRNA Ser together with tRNase Z L works as a sequence-specific RNA cutter

Abstract A complex of the 3′-truncated tRNAArg that lacks 9 nt and tRNase ZL works as a GCCC-recognizing RNA cutter. It recognizes an RNA substrate via four Watson-Crick-Franklin base-pairings with the 3′-truncated tRNAArg. Human SLFN11 and SLFN13 can generate 3′-truncated tRNALeu that lacks 10 nt and 3′-truncated tRNASer that lacks 11 nt, respectively, from their corresponding mature tRNAs. Here, we investigated if these 3′-truncated tRNAs together with tRNase ZL work as sequence-specific RNA cutters. We examined five RNA targets for cleavage by recombinant human tRNase ZL in the presence of the 3′-truncated tRNALeu or tRNASer. We demonstrated that the 3′-truncated tRNALeu and tRNASer together with tRNase ZL indeed work as ∼6-base-recognizing and 7-base-recognizing RNA cutters, respectively. Competing Interest Statement MN is an advisor of Veritas In Silico Inc., and owns stock of the company.