ELAC1 selectively trims vault RNA 3′ ends, revealing substrate partitioning between human RNase Z paralogs

ABSTRACT: Ribonuclease Z enzymes remove 3′ trailers from precursor tRNAs. In human cells, ELAC2/RNase ZL matures nuclear and mitochondrial pre-tRNAs and releases the tRNA-like small RNAs mascRNA and menRNA from the 3′ ends of MALAT1 and NEAT1. Instead, the cytosolic short paralog ELAC1/RNase ZS repairs ANKZF1-cleaved tRNAs, with its wider substrate repertoire remaining unresolved. Here, we investigate the role of ELAC1 in RNA metabolism using transcriptome profiling, small RNA sequencing, CLIP-seq, and biochemical reconstitution. ELAC1 is dispensable for canonical tRNA processing but it is associated with structured RNA polymerase III transcripts, prominently Y RNAs and vault RNAs (vtRNAs). Purified ELAC1 cleaved all four human vtRNAs near their 3′ ends, and catalytically inactive ELAC1 in vivo binds precursor vtRNAs carrying 3′ oligoU trailers. High-resolution mapping placed the vtRNA1-2 site immediately after U86, the first residue of the 3′ extension that follows the terminal stem, and the equivalent position in each other paralog. A distal P4 element and an intact terminal stem were required for efficient cleavage. ELAC2 showed little or no vtRNA cleavage under the conditions tested, and processed pre-tRNA with stricter site selection. Loss and re-expression of ELAC1 altered structured ncRNA abundance and small-RNA end profiles. These data identify vtRNAs as direct biochemical substrates of ELAC1 and support a division of labor where ELAC2 is optimized for high-fidelity pre-tRNA maturation while ELAC1 acts on a broader range of structured RNA ends.

ORGANISM(S): Homo sapiens

PROVIDER: GSE348566 | GEO | 2026/09/28

REPOSITORIES: GEO