Affinage

RPP30

Ribonuclease P protein subunit p30 · UniProt P78346

Round 2 corrected
Length
268 aa
Mass
29.3 kDa
Annotated
2026-04-28
40 papers in source corpus 6 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPP30 is a protein subunit of the RNase P/MRP ribonucleoprotein complex that plays essential roles in pre-tRNA 5'-leader processing and endoribonucleolytic cleavage of m6A-modified mRNAs and circular RNAs. RPP30 adopts a TIM-barrel fold and forms a heterotetrameric subcomplex with Pop5 (two copies each), in which RPP30 shields hydrophobic surfaces of Pop5 to stabilize its active conformation and enable the tetramer to engage stem-loops SL3 and SL16 of RNase P RNA, thereby activating the catalytic C-domain for pre-tRNA cleavage (PMID:20139629, PMID:22162665, PMID:26152732, PMID:25704799). Beyond canonical tRNA maturation, the human RNase P/MRP complex containing RPP30 is recruited by the m6A-reader YTHDF2 through the adaptor HRSP12 to perform endoribonucleolytic cleavage of m6A-containing transcripts, establishing a non-canonical RNA decay pathway (PMID:30930054).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2006 Medium

    Identification of a Dictyostelium Rpp30 homolog that co-purifies with RNase P and binds its RNA subunit extended the known phylogenetic range of RPP30 as an integral RNase P component with a conserved TIM-barrel fold.

    Evidence Immunochemical co-purification with active RNase P fractions and in vitro RNA-binding assay in D. discoideum

    PMID:17207566

    Open questions at the time
    • Single study without reciprocal validation
    • No stoichiometric or structural data for the eukaryotic complex at this stage
  2. 2010 High

    Domain-swap experiments established that the Pop5–Rpp30 pair specifically activates the catalytic C-domain of RNase P RNA, resolving which protein subunits control which functional domain of the ribozyme.

    Evidence Chimeric archaeal/bacterial RNase P RNA reconstitution with in vitro pre-tRNA cleavage assays

    PMID:20139629

    Open questions at the time
    • Mechanism by which Pop5–Rpp30 contacts the C-domain RNA was not resolved at atomic level
    • Whether human RPP30 functions identically was not directly tested
  3. 2011 High

    Biophysical characterization revealed that RPP30 adopts a TIM-barrel fold and forms a tight heterotetrameric complex with Pop5 (2:2 stoichiometry), defining the minimal assembly unit for C-domain activation.

    Evidence NMR backbone assignments, chemical shift perturbation mapping, ITC, SEC, and light scattering on archaeal Rpp30–Pop5

    PMID:22162665

    Open questions at the time
    • Exact RNA-binding interface of the heterotetramer was not mapped
    • Human complex stoichiometry not directly confirmed
  4. 2015 High

    Crystal structures of Rpp30 alone and in complex with Pop5, combined with SPR binding studies, showed that Rpp30 stabilizes Pop5's α4 helix — the key RNA-recognition element — enabling the tetramer to bridge stem-loops SL3 and SL16 for C-domain activation.

    Evidence X-ray crystallography of archaeal Rpp30 and Rpp30–Pop5 complex; SPR with Pop5 mutants; cross-species reconstitution assays

    PMID:25704799 PMID:26152732

    Open questions at the time
    • High-resolution structure of the full RNase P holoenzyme with RNA was not yet available
    • Whether the SL3/SL16-bridging model applies to the human complex is inferred, not demonstrated
  5. 2019 High

    Discovery that the human RNase P/MRP complex (containing RPP30) functions in m6A-dependent mRNA and circRNA decay — recruited by YTHDF2 via HRSP12 — expanded RPP30's role beyond tRNA processing to a regulated mRNA turnover pathway.

    Evidence Co-immunoprecipitation, in vitro cleavage assays, transcriptome-wide RNA-seq and CLIP-seq in human cells

    PMID:30930054

    Open questions at the time
    • Whether RPP30 has a specific or essential role within the complex for m6A-RNA cleavage, versus being a structural subunit, is unresolved
    • Structural basis for HRSP12-mediated recruitment of RNase P/MRP is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the human RNase P holoenzyme with its RNA subunit, and direct dissection of RPP30's individual contribution to m6A-RNA cleavage versus tRNA processing, remain open questions.
  • No structure of human RPP30 in the context of the full holoenzyme–substrate complex
  • Distinct or overlapping functions of RPP30 in tRNA processing versus m6A-RNA decay not separated genetically
  • Regulation of RPP30 expression or post-translational modification is uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-8953854 Metabolism of RNA 2
Partners
HRSP12POP5YTHDF2
Complex memberships
RNase MRPRNase P

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Archaeal RNase P protein homologs Pop5 and Rpp30 (from Pyrococcus horikoshii) function equivalently to the bacterial C5 protein in activating the catalytic RNA C-domain of RNase P, while Rpp21 and Rpp29 are implicated in stabilization of the S-domain. This was demonstrated using chimeric RNase P RNAs in which C- and S-domains of E. coli M1 RNA and P. horikoshii RNA were exchanged, and reconstitution assays with pre-tRNA cleavage activity. Chimeric RNA reconstitution assay, in vitro pre-tRNA cleavage activity Bioscience, biotechnology, and biochemistry High 20139629
2011 Archaeal RPP30 and Pop5 (from Pyrococcus furiosus) form a tight 1:1 protein-protein interaction with net heterotetramer stoichiometry (two copies each of Pop5 and RPP30, ~78 kDa). NMR chemical shift perturbation mapping revealed the binding surface of Pop5 on RPP30. RPP30 is well-structured in solution with a TIM-barrel fold. ITC confirmed tight binding with complex isotherms indicating higher-order assembly. NMR spectroscopy (backbone assignments + chemical shift perturbation), isothermal titration calorimetry (ITC), size-exclusion chromatography, light scattering Archaea (Vancouver, B.C.) High 22162665
2015 The archaeal Pop5-Rpp30 heterotetramer (PhoRpp30-(PhoPop5)2-PhoRpp30) strongly interacts with the stem-loop SL3 of RNase P RNA (PhopRNA), whereas Pop5 alone has markedly reduced affinity and Rpp30 alone has little affinity to SL3. The C-terminal helix (α4) of Pop5 functions as the molecular recognition element for SL3. Rpp30 assists Pop5 in attaining a functionally active conformation by shielding hydrophobic surfaces, enabling the tetramer to bridge SL3 and SL16 in PhopRNA for C-domain activation. Surface plasmon resonance (SPR) with Pop5 mutants, gel filtration chromatography Journal of biochemistry High 26152732
2006 A Dictyostelium discoideum Rpp30 homolog (DRpp30, 40.7 kDa) co-purifies with RNase P holoenzyme and can bind both D. discoideum RNase P RNA and tRNA transcripts in vitro. Homology modeling indicates DRpp30 adopts a TIM-barrel fold, consistent with archaeal and human Rpp30 structures. Immunochemical analysis of RNase P active fractions, in vitro RNA-binding assay, homology modeling Biochimie Medium 17207566
2015 Archaeal Rpp30 from Thermococcus kodakarensis (TkoRpp30) adopts a TIM-barrel fold and forms a complex with TkoPop5, as determined by crystal structures of TkoRpp30 alone and in complex with TkoPop5. Reconstitution experiments showed that TkoRpp30 can substitute for PhoRpp30 in P. horikoshii RNase P with slightly reduced pre-tRNA cleavage activity, confirming functional and structural conservation of Rpp30 across archaea. X-ray crystallography (crystal structures of Rpp30 alone and in complex with Pop5), in vitro pre-tRNA cleavage reconstitution assay Bioscience, biotechnology, and biochemistry High 25704799
2019 Human RNase P/MRP complex (of which RPP30 is a protein subunit) mediates endoribonucleolytic cleavage of m6A-containing RNAs. YTHDF2 (m6A reader) recruits RNase P/MRP via the adaptor protein HRSP12, which bridges YTHDF2 and RNase P/MRP to elicit rapid degradation of m6A-modified RNAs, including a subset of circular RNAs. Transcriptome-wide analyses identified HRSP12-binding sites and RNase P/MRP-directed cleavage sites flanking YTHDF2-binding sites. Co-immunoprecipitation, in vitro cleavage assays, transcriptome-wide RNA-seq, CLIP-seq, domain-mapping experiments Molecular cell High 30930054

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 Identification and characterization of essential genes in the human genome. Science (New York, N.Y.) 1236 26472758
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2005 Nucleolar proteome dynamics. Nature 934 15635413
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2015 Gene essentiality and synthetic lethality in haploid human cells. Science (New York, N.Y.) 657 26472760
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2019 Endoribonucleolytic Cleavage of m6A-Containing RNAs by RNase P/MRP Complex. Molecular cell 483 30930054
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2018 DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Cell 379 29656893
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
2005 A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. American journal of human genetics 137 16385451
2010 RioK1, a new interactor of protein arginine methyltransferase 5 (PRMT5), competes with pICln for binding and modulates PRMT5 complex composition and substrate specificity. The Journal of biological chemistry 131 21081503
2018 Normalization of cell associated antiretroviral drug concentrations with a novel RPP30 droplet digital PCR assay. Scientific reports 24 29483619
2021 The rice RNase P protein subunit Rpp30 confers broad-spectrum resistance to fungal and bacterial pathogens. Plant biotechnology journal 23 33932077
2010 Archaeal homologs of human RNase P protein pairs Pop5 with Rpp30 and Rpp21 with Rpp29 work on distinct functional domains of the RNA subunit. Bioscience, biotechnology, and biochemistry 18 20139629
2020 RPP30, a transcriptional regulator, is a potential pathogenic factor in glioblastoma. Aging 9 32702667
2011 Assembly of the complex between archaeal RNase P proteins RPP30 and Pop5. Archaea (Vancouver, B.C.) 7 22162665
2015 Functional implication of archaeal homologues of human RNase P protein pair Pop5 and Rpp30. Journal of biochemistry 5 26152732
2015 On archaeal homologs of the human RNase P proteins Pop5 and Rpp30 in the hyperthermophilic archaeon Thermococcus kodakarensis. Bioscience, biotechnology, and biochemistry 4 25704799
2006 A 40.7 kDa Rpp30/Rpp1 homologue is a protein subunit of Dictyostelium discoideum RNase P holoenzyme. Biochimie 4 17207566
2026 Dual regulation of RNase P subunit Rpp30 by an acetyltransferase and E3 ligase in rice immunity. Plant physiology 0 41873718
2025 Validation on the First-Tier Fully Automated High-Throughput SMN1, SMN2, TREC, and RPP30 Quantification by Quadruplex Droplet Digital PCR for Newborn Screening for Spinal Muscular Atrophy and Severe Combined Immunodeficiency. International journal of neonatal screening 0 41133709