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Cited by 7RNA and protein synthesis mechanismsRNA Research and SplicingNuclear Structure and Function

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Composition and RNA binding specificity of metazoan RNase MRP

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Liu, Yuan, He, Shiyang, Pyo, Kawon, Zheng, Shanshan, Chen, Meijuan, Braschi, Bryony, Cheloufi, Sihem, Slavov, Nikolai, Marzluff, William F, Murn, Jernej·2025·Nucleic Acids Research
DOI 10.1093/nar/gkaf829PMC PMC12390755

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Abstract

Ribonuclease (RNase) MRP is a conserved RNA-based enzyme best known for its essential role in the maturation of ribosomal RNA (rRNA) in eukaryotes. However, the composition and RNA substrate specificity of this multisubunit ribonucleoprotein complex in higher eukaryotes remain a mystery. Here, we identify NEPRO and C18ORF21 (which we renamed RMP64 and RMP24, respectively) as constitutive subunits of metazoan RNase MRP. These proteins are unique to RNase MRP and absent from the closely related RNase P, which processes transfer RNA (tRNA) precursors and tRNA-like substrates. We find that RMP64 and RMP24 are integral subunits of RNase MRP, stabilize its catalytic RNA, and are required for rRNA maturation and cell proliferation. Leveraging these discoveries, we identify a broad suite of in vivo RNA-binding targets of each enzyme, including potential cleavage sites at nucleotide resolution. Our findings identify the first metazoan RNase MRP-specific protein subunits and define the RNA-targeting repertoire of this essential enzyme in mammalian cells.

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Metadata

Authors
Liu, Y., He, S., Pyo, K., Zheng, S., Chen, M., Braschi, B., Cheloufi, S., Slavov, N., Marzluff, W. F., & Murn, J.
Affiliations
  • University of California, Riverside (US)
  • Northeastern University (US)
  • University of Cambridge (GB)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Murn, Jernej
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2025-08-27
Volume
53
Issue
16
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkaf829
PMC
PMC12390755
OpenAlex
W4413768522
Cited by
7
References
4
Citations by year
2026: 5 · 2025: 2
FWCI
2.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. National Science Foundation (2054195)
  • NIGMS
  • National Institutes of Health (R35GM148218, GM144693, GM151004, U24HG003345)
  • California Institute of Regenerative Medicine (EDUC4-12752)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
RNase MRP, ribonuclease P, ribosomal RNA maturation, protein subunit composition, RNA binding specificity, RNA cleavage sites, ribozymes, ribonucleoprotein complexes, cell proliferation
MeSH terms
Animals, Endoribonucleases, Humans, RNA Precursors, RNA, Ribosomal, RNA, Transfer, Substrate Specificity, RNA, Catalytic, Mitochondrial Proteins, Ribonuclease P, Cell Proliferation

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