Identification of RMP24 and RMP64, human ribonuclease MRP-specific protein components

Rui Che; Bhoomi Mirani; Monireh Panah; Xiaotong Chen; Hong Luo; Andrei Alexandrov

doi:10.1016/j.celrep.2025.115752

Cell Reports (Jun 2025)

Identification of RMP24 and RMP64, human ribonuclease MRP-specific protein components

Rui Che,
Bhoomi Mirani,
Monireh Panah,
Xiaotong Chen,
Hong Luo,
Andrei Alexandrov

Affiliations

Rui Che: Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29631, USA; Clemson University Center for Human Genetics, Greenwood, SC 29646, USA
Bhoomi Mirani: Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29631, USA; Clemson University Center for Human Genetics, Greenwood, SC 29646, USA
Monireh Panah: Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29631, USA; Clemson University Center for Human Genetics, Greenwood, SC 29646, USA
Xiaotong Chen: Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29631, USA
Hong Luo: Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29631, USA
Andrei Alexandrov: Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29631, USA; Clemson University Center for Human Genetics, Greenwood, SC 29646, USA; Corresponding author

DOI: https://doi.org/10.1016/j.celrep.2025.115752
Journal volume & issue: Vol. 44, no. 6
p. 115752

Abstract

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Summary: Human RNase MRP is a ribonucleoprotein (RNP) enzyme that processes precursor rRNA (pre-rRNA) at ITS1 site 2 and may have additional activities. It is an endonuclease related to RNase P, which processes pre-tRNAs and pre-tRNA-like substrates. In Saccharomyces cerevisiae, these two RNPs utilize distinct catalytic RNAs with eight shared and one or two specific protein subunits. However, the human RNase MRP-specific protein subunits remain unidentified. Our genome-wide forward genetic screening identifies two poorly characterized human genes, which we name ribonuclease MRP subunit P24 (RMP24) and RMP64. We show that Rmp24 and Rmp64 are required for pre-rRNA ITS1 site 2 processing and associate with MRP RNA but are not required for RNase P activity and do not associate with RNase P-specific H1 RNA. Despite limited sequence homology, Rmp24 and Rmp64 exhibit predicted structural similarities to two RNase MRP-specific components in S. cerevisiae. Collectively, our functional screening and validation reveal two protein components unique to human nuclear RNase MRP.

CP: Molecular biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.cell.com/cell-reports/home

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