PreprintCited by 0RNA 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, Anzie, Zheng, Shanshan, Chen, Meijuan, Cheloufi, Sihem, Slavov, Nikolai, Marzluff, William F, Murn, Jernej·2025·bioRxiv (Cold Spring Harbor Laboratory)

Preprint — published as 10.1093/nar/gkaf829 · Paper page

Abstract

Ribonuclease (RNase) MRP is a conserved RNA-based enzyme that is essential for 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 as constitutive subunits of metazoan RNase MRP. Both proteins are specific to RNase MRP and are the only ones distinguishing this enzyme from the closely related RNase P, which selectively cleaves transfer RNA-like substrates. We find that NEPRO and C18ORF21 each form a complex with all other subunits of RNase MRP, stabilize its catalytic RNA, and are required for rRNA maturation and cell proliferation. We harness our discovery to identify a full suite of in vivo RNA targets of each enzyme, including positions of potential cleavage sites at nucleotide resolution. These findings resolve the general composition of metazoan RNase MRP, illuminate its RNA binding specificity, and provide valuable assets for functional exploration of this essential eukaryotic enzyme.

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Metadata

Authors
Liu, Y., He, S., Pyo, A., Zheng, S., Chen, M., Cheloufi, S., Slavov, N., Marzluff, W. F., & Murn, J.
Affiliations
  • University of California, Riverside (US)
  • Northeastern University (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Murn, Jernej
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2025-02-23
OpenAlex
W4407869485
Cited by
0
References
2
Type
posted content
Language
en
Open access
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
Funders
National Institute of General Medical Sciences (R01GM144693, R35GM151004, R35GM148218)
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, enzyme subunit composition, RNA binding specificity, ribozymes, cleavage site, cell proliferation

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