Structural basis of transfer RNA processing by bacterial minimal RNase P

Abstract Precursor tRNAs (pre-tRNAs) require nucleolytic removal of 5′-leader and 3′-trailer sequences for maturation, which is essential for proper tRNA function. The endoribonuclease RNase P exists in diverse forms, including RNA- and protein-based RNase P, and removes 5′-leader sequences from pre...

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Main Authors: Takamasa Teramoto, Takeshi Koyasu, Takashi Yokogawa, Naruhiko Adachi, Kouta Mayanagi, Takahiro Nakamura, Toshiya Senda, Yoshimitsu Kakuta
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60002-1
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author Takamasa Teramoto
Takeshi Koyasu
Takashi Yokogawa
Naruhiko Adachi
Kouta Mayanagi
Takahiro Nakamura
Toshiya Senda
Yoshimitsu Kakuta
author_facet Takamasa Teramoto
Takeshi Koyasu
Takashi Yokogawa
Naruhiko Adachi
Kouta Mayanagi
Takahiro Nakamura
Toshiya Senda
Yoshimitsu Kakuta
author_sort Takamasa Teramoto
collection DOAJ
description Abstract Precursor tRNAs (pre-tRNAs) require nucleolytic removal of 5′-leader and 3′-trailer sequences for maturation, which is essential for proper tRNA function. The endoribonuclease RNase P exists in diverse forms, including RNA- and protein-based RNase P, and removes 5′-leader sequences from pre-tRNAs. Some bacteria and archaea possess a unique minimal protein-based RNase P enzyme, HARP, which forms dodecamers with twelve active sites. Here, we present cryogenic electron microscopy structures of HARP dodecamers complexed with five pre-tRNAs, and we show that HARP oligomerization enables specific recognition of the invariant distance between the acceptor stem 5′-end and the TψC-loop, functioning as a molecular ruler—a feature representing convergent evolution among RNase P enzymes. The HARP dodecamer uses only five active sites for 5′-leader cleavage, while we identify a 3′-trailer cleavage activity in the remaining seven sites. This elucidation reveals how small proteins evolve through oligomerization to adapt a pivotal biological function (5′-leader processing) and acquire a novel function (3′-trailer processing).
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spelling doaj-art-36e636f35488409ca24e17c5e10ab3ab2025-08-20T03:37:37ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-60002-1Structural basis of transfer RNA processing by bacterial minimal RNase PTakamasa Teramoto0Takeshi Koyasu1Takashi Yokogawa2Naruhiko Adachi3Kouta Mayanagi4Takahiro Nakamura5Toshiya Senda6Yoshimitsu Kakuta7Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu UniversityLaboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu UniversityFaculty of Engineering, Gifu UniversityStructural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK)Department of Drug Discovery Structural Biology, Faculty of Pharmaceutical Sciences, Kyushu UniversityLaboratory of Genome Chemistry and Engineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu UniversityStructural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK)Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu UniversityAbstract Precursor tRNAs (pre-tRNAs) require nucleolytic removal of 5′-leader and 3′-trailer sequences for maturation, which is essential for proper tRNA function. The endoribonuclease RNase P exists in diverse forms, including RNA- and protein-based RNase P, and removes 5′-leader sequences from pre-tRNAs. Some bacteria and archaea possess a unique minimal protein-based RNase P enzyme, HARP, which forms dodecamers with twelve active sites. Here, we present cryogenic electron microscopy structures of HARP dodecamers complexed with five pre-tRNAs, and we show that HARP oligomerization enables specific recognition of the invariant distance between the acceptor stem 5′-end and the TψC-loop, functioning as a molecular ruler—a feature representing convergent evolution among RNase P enzymes. The HARP dodecamer uses only five active sites for 5′-leader cleavage, while we identify a 3′-trailer cleavage activity in the remaining seven sites. This elucidation reveals how small proteins evolve through oligomerization to adapt a pivotal biological function (5′-leader processing) and acquire a novel function (3′-trailer processing).https://doi.org/10.1038/s41467-025-60002-1
spellingShingle Takamasa Teramoto
Takeshi Koyasu
Takashi Yokogawa
Naruhiko Adachi
Kouta Mayanagi
Takahiro Nakamura
Toshiya Senda
Yoshimitsu Kakuta
Structural basis of transfer RNA processing by bacterial minimal RNase P
Nature Communications
title Structural basis of transfer RNA processing by bacterial minimal RNase P
title_full Structural basis of transfer RNA processing by bacterial minimal RNase P
title_fullStr Structural basis of transfer RNA processing by bacterial minimal RNase P
title_full_unstemmed Structural basis of transfer RNA processing by bacterial minimal RNase P
title_short Structural basis of transfer RNA processing by bacterial minimal RNase P
title_sort structural basis of transfer rna processing by bacterial minimal rnase p
url https://doi.org/10.1038/s41467-025-60002-1
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