Structure and mechanistic features of the prokaryotic minimal RNase P
Abstract
Endonucleolytic removal of 5’-leader sequences from tRNA precursor transcripts (pre-tRNAs) by RNase P is essential for protein synthesis. Beyond RNA-based RNase P enzymes, protein-only versions of the enzyme exert this function in various Eukarya (there termed PRORPs) and in some bacteria ( Aquifex aeolicus and close relatives); both enzyme types belong to distinct subgroups of the PIN domain metallonuclease superfamily. Homologs of Aquifex RNase P (HARPs) are also expressed in some other bacteria and many archaea, where they coexist with RNA-based RNase P and do not represent the main RNase P activity. Here we solved the structure of the bacterial HARP from Halorhodospira halophila by cryo-EM revealing a novel screw-like dodecameric assembly. Biochemical experiments demonstrate that oligomerization is required for RNase P activity of HARPs. We propose that the tRNA substrate binds to an extended spike-helix (SH) domain that protrudes from the screw-like assembly to position the 5’-end in close proximity to the active site of the neighboring dimer subunit. The structure suggests that eukaryotic PRORPs and prokaryotic HARPs recognize the same structural elements of pre-tRNAs (tRNA elbow region and cleavage site). Our analysis thus delivers the structural and mechanistic basis for pre-tRNA processing by the prokaryotic HARP system.
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BibTeX
@article{feyh2026structure,
title = {{Structure and mechanistic features of the prokaryotic minimal RNase P}},
author = {Rebecca Feyh and Nadine B Waeber and Simone Prinz and Pietro Ivan Giammarinaro and Gert Bange and Georg Hochberg and Roland K Hartmann and Florian Altegoer},
journal = {eLife},
year = {2026},
month = oct,
doi = {10.7554/elife.70160},
url = {https://hal.science/hal-05780522v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Structure and mechanistic features of the prokaryotic minimal RNase P
AU - Rebecca Feyh
AU - Nadine B Waeber
AU - Simone Prinz
AU - Pietro Ivan Giammarinaro
AU - Gert Bange
AU - Georg Hochberg
AU - Roland K Hartmann
AU - Florian Altegoer
PY - 2026
DA - 2026/10/06
JO - eLife
DO - 10.7554/elife.70160
UR - https://hal.science/hal-05780522v1
AB - Endonucleolytic removal of 5’-leader sequences from tRNA precursor transcripts (pre-tRNAs) by RNase P is essential for protein synthesis. Beyond RNA-based RNase P enzymes, protein-only versions of the enzyme exert this function in various Eukarya (there termed PRORPs) and in some bacteria ( Aquifex aeolicus and close relatives); both enzyme types belong to distinct subgroups of the PIN domain metallonuclease superfamily. Homologs of Aquifex RNase P (HARPs) are also expressed in some other bacteria and many archaea, where they coexist with RNA-based RNase P and do not represent the main RNase P activity. Here we solved the structure of the bacterial HARP from Halorhodospira halophila by cryo-EM revealing a novel screw-like dodecameric assembly. Biochemical experiments demonstrate that oligomerization is required for RNase P activity of HARPs. We propose that the tRNA substrate binds to an extended spike-helix (SH) domain that protrudes from the screw-like assembly to position the 5’-end in close proximity to the active site of the neighboring dimer subunit. The structure suggests that eukaryotic PRORPs and prokaryotic HARPs recognize the same structural elements of pre-tRNAs (tRNA elbow region and cleavage site). Our analysis thus delivers the structural and mechanistic basis for pre-tRNA processing by the prokaryotic HARP system.
SN - 2050-084X
ER -