Affinage

RPP40

Ribonuclease P protein subunit p40 · UniProt O75818

Length
363 aa
Mass
41.8 kDa
Annotated
2026-04-28
10 papers in source corpus 6 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPP40 is a protein subunit shared by the human RNase P and RNase MRP ribonucleoprotein complexes, functioning in pre-tRNA and pre-rRNA processing. It was identified as a bona fide RNase P component through co-purification and immunoprecipitation of catalytically active holoenzyme (PMID:9630247, PMID:10024167), and participates in extensive protein–protein interactions with subunits including hPop1, Rpp21, Rpp29, Rpp30, and Rpp38, as well as direct contacts with RNase MRP RNA, contributing to the architectural assembly of both complexes (PMID:11158571, PMID:15096576). Glycerol gradient sedimentation confirms RPP40 co-sediments with both 12S and 60–80S RNase MRP/P particles, establishing it as a constitutive shared subunit rather than a complex-specific factor (PMID:16723659).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 1998 High

    Establishing RPP40 as a genuine RNase P subunit resolved the identity of proteins required for human nuclear pre-tRNA processing beyond the catalytic RNA.

    Evidence Co-purification and immunoprecipitation of catalytically active RNase P holoenzyme using anti-Rpp40 antibodies from HeLa cell extracts

    PMID:9630247

    Open questions at the time
    • Role of RPP40 in catalysis versus holoenzyme stability not distinguished
    • Stoichiometry of RPP40 within the holoenzyme unknown
  2. 1999 High

    Confirmation that RPP40 is one of at least eight protein subunits of RNase P solidified the multi-subunit composition of the human enzyme.

    Evidence Immunoprecipitation of catalytically active RNase P from HeLa cells with antibodies against individual recombinant subunits

    PMID:10024167

    Open questions at the time
    • Whether RPP40 is essential for catalytic activity or dispensable for in vitro cleavage not tested
    • Structural arrangement of RPP40 relative to H1 RNA not resolved
  3. 2001 Medium

    Mapping RPP40's protein–protein interaction network within RNase P revealed how multiple direct contacts (with hPop1, Rpp21, Rpp29, Rpp30, Rpp38) contribute to holoenzyme assembly.

    Evidence Yeast two-hybrid screens using HeLa cDNA library

    PMID:11158571

    Open questions at the time
    • Interactions described as weak in yeast two-hybrid; not all validated by orthogonal pulldown
    • Which interactions are essential for holoenzyme integrity versus redundant not determined
  4. 2004 Medium

    Demonstrating that RPP40 contacts both protein subunits and the RNA component of RNase MRP established it as a dual-complex subunit with direct RNA-binding capacity.

    Evidence GST pull-down experiments with mutant RNase MRP RNAs mapping protein–protein and protein–RNA contacts

    PMID:15096576

    Open questions at the time
    • Specific RNA elements or nucleotides contacted by RPP40 not mapped at high resolution
    • Whether RPP40 RNA contacts are required for MRP catalytic function not tested
  5. 2006 Medium

    Sedimentation analysis showing RPP40 co-fractionates with both 12S and 60–80S particles distinguished it as a constitutive shared subunit of RNase P and RNase MRP, unlike complex-specific factors.

    Evidence Glycerol gradient sedimentation combined with coimmunoprecipitation of VSV-epitope-tagged subunits

    PMID:16723659

    Open questions at the time
    • Nature of the 60–80S particles containing RPP40 not fully characterized
    • Whether RPP40 partitions between the two complexes dynamically or is simultaneously present in both not resolved
  6. 2025 Low

    Loss-of-function studies in hepatocellular carcinoma cells linked RPP40 to coordination of pre-rRNA transcription and ribosomal protein gene expression, extending its role beyond RNA processing to ribosome biogenesis control in cancer.

    Evidence Knockdown and overexpression in HCC cell lines with proliferation, migration, and invasion assays plus transcriptional profiling

    PMID:40517827

    Open questions at the time
    • Single-lab study in one cancer type without in vivo validation
    • Mechanism by which RPP40 influences pre-rRNA transcription (direct versus indirect) not defined
    • Whether ribosome biogenesis phenotype reflects canonical RNase MRP/P function or a moonlighting activity is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RPP40 contributes to catalytic activity of RNase P and RNase MRP — whether it is essential for substrate recognition, cleavage chemistry, or structural integrity — remains mechanistically undefined.
  • No reconstitution experiment testing RPP40's necessity for in vitro catalysis
  • No high-resolution structure of human RNase P or MRP with RPP40 resolved
  • No in vivo depletion study examining pre-tRNA or pre-rRNA processing defects in human cells

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-8953854 Metabolism of RNA 4
Partners
POP1RPP21RPP29RPP30RPP38
Complex memberships
RNase MRPRNase P

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 RPP40 (Rpp40) was identified as a protein subunit that co-purifies with catalytically active human RNase P holoenzyme; polyclonal antibodies against recombinant Rpp40 precipitate active holoenzyme, establishing it as a bona fide component of the RNase P ribonucleoprotein complex. Co-purification, immunoprecipitation of active holoenzyme with polyclonal antibodies against recombinant Rpp40 RNA (New York, N.Y.) High 9630247
1999 Rpp40 is one of at least eight protein subunits of the human RNase P tRNA processing enzyme in HeLa cells, as confirmed by immunoprecipitation of catalytically active RNase P. Immunoprecipitation of catalytically active RNase P from HeLa cells using antibodies against recombinant protein subunits RNA (New York, N.Y.) High 10024167
2001 Rpp40 participates in extensive protein-protein interactions with other subunits of human nuclear RNase P (including hPop1, Rpp21, Rpp29, Rpp30, and Rpp38), contributing to holoenzyme assembly. Yeast two-hybrid system with HeLa cell cDNA library Proceedings of the National Academy of Sciences of the United States of America Medium 11158571
2004 Rpp40 forms direct protein-protein interactions with multiple RNase MRP subunits and directly contacts the RNase MRP RNA, as part of a network of 19 direct protein-protein and 6 direct protein-RNA interactions that define the architecture of the human RNase MRP complex. GST pull-down experiments for protein-protein and protein-RNA interactions; analysis of mutant RNase MRP RNAs Nucleic acids research Medium 15096576
2006 Rpp40 is associated with both RNase MRP and RNase P complexes, and co-sediments with both 12S and 60–80S fractions, indicating it is a shared subunit likely present in all RNase MRP particles, in contrast to subunits that are RNase P-specific. Glycerol gradient sedimentation and coimmunoprecipitation with VSV-epitope-tagged subunits RNA (New York, N.Y.) Medium 16723659
2025 RPP40 promotes HCC cell proliferation, migration, and invasion by coordinating transcription of pre-rRNA and expression of ribosomal protein genes, linking its RNase P/MRP function to ribosome biogenesis control in cancer cells. Loss-of-function and overexpression in HCC cell lines with phenotypic readouts (proliferation, migration, invasion assays) and transcriptional analysis of rRNA and ribosomal protein genes Gene Low 40517827

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Mutual interactions between subunits of the human RNase MRP ribonucleoprotein complex. Nucleic acids research 84 15096576
1998 Autoantigenic properties of some protein subunits of catalytically active complexes of human ribonuclease P. RNA (New York, N.Y.) 52 9630247
2001 Protein-protein interactions with subunits of human nuclear RNase P. Proceedings of the National Academy of Sciences of the United States of America 51 11158571
1999 Rpp14 and Rpp29, two protein subunits of human ribonuclease P. RNA (New York, N.Y.) 48 10024167
2002 Purification and characterization of Rpp25, an RNA-binding protein subunit of human ribonuclease P. RNA (New York, N.Y.) 47 12003489
2006 Differential association of protein subunits with the human RNase MRP and RNase P complexes. RNA (New York, N.Y.) 44 16723659
2020 The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles. Cancers 40 32512867
2014 An immunohistochemical analysis of a newly developed, mouse monoclonal p40 (BC28) antibody in lung, bladder, skin, breast, prostate, and head and neck cancers. Archives of pathology & laboratory medicine 31 24528495
2023 Effect of Demographics and Time to Sample Processing on the qPCR Detection of Pathogenic Leptospira spp. from Human Samples in the National Reference Laboratory for Leptospirosis, Brazil. Tropical medicine and infectious disease 3 36977152
2025 Ribonuclease P/MRP subunit RPP40 coordinates the transcription of pre-rRNA and ribosomal protein genes to promote Hepatocellular carcinoma malignancy. Gene 1 40517827