Affinage

POP7

Ribonuclease P protein subunit p20 · UniProt O75817

Length
140 aa
Mass
15.7 kDa
Annotated
2026-04-28
12 papers in source corpus 9 papers cited in narrative 9 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POP7 (also known as Rpp20; yeast ortholog Rpp2/Pop7) is an obligate subunit of both RNase P and RNase MRP ribonucleoprotein complexes, where it functions in tRNA 5'-leader processing and pre-rRNA maturation. POP7 forms a salt-resistant heterodimer with Rpp25 (Pop6 in yeast) through their conserved Alba-type core domains; neither subunit alone binds the P3 RNA domain of RNase MRP/P with appreciable affinity, but the 1:1 heterodimer engages the P3 internal loop and distal stem via a conserved positively charged surface with nanomolar affinity, and this interaction is required for catalytic activity and nucleolar localization (PMID:17717080, PMID:20215441, PMID:33571640). Crystal structures of the free heterodimer and its ternary complex with the RMRP P3 domain reveal quaternary-level divergence from archaeal Alba homodimers that underlies single-stranded RNA recognition specificity, and show that disease-causing RMRP mutations cluster at the protein–RNA interface (PMID:29625199, PMID:33571640). Beyond its canonical ribonuclease roles, POP7 binds intronic regions of mRNAs and stabilizes ILF3 mRNA to promote breast cancer cell proliferation and invasion (PMID:35579257).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1998 High

    Establishing POP7 (Rpp2) as an essential subunit of both RNase P and RNase MRP resolved that the same protein participates in tRNA 5'-end processing and pre-rRNA maturation.

    Evidence Epitope-tagged immunoprecipitation, in vivo depletion, and in vitro cleavage assays in yeast

    PMID:9618478

    Open questions at the time
    • Mechanism by which Rpp2 contributes to catalysis was unknown
    • Direct RNA-binding site not identified
    • Physical partners within the holoenzyme not mapped
  2. 2004 Medium

    Identification of SMN as a physical interaction partner of POP7 raised the possibility that RNase P/MRP components participate in stress-granule biology or SMN-dependent pathways.

    Evidence Yeast two-hybrid, in vitro binding, co-immunoprecipitation, and immunofluorescence in human cells

    PMID:14715275

    Open questions at the time
    • Interaction mapped only on the SMN side (exons 3–4); POP7 binding determinants undefined
    • Functional consequence of POP7–SMN interaction not established
    • Not independently replicated
  3. 2006 High

    Demonstrating that Rpp20 and Rpp25 form a stable obligate heterodimer whose assembly is prerequisite for P3 RNA binding and nucleolar localization explained how two individually weak RNA-binding proteins achieve high-affinity recognition and co-regulate each other's stability.

    Evidence Co-immunoprecipitation, gel filtration, RNA binding assays, immunofluorescence, knockdown/overexpression in human cells

    PMID:17119099

    Open questions at the time
    • Structural basis of heterodimerization unknown
    • Whether dimerization is sufficient for holoenzyme assembly not tested
  4. 2007 High

    Footprinting of the yeast Pop6–Pop7 complex on P3 RNA revealed that the heterodimer induces local structural rearrangement of the P3 loop, suggesting it primes the RNA for recruitment of additional protein subunits.

    Evidence Recombinant protein expression, gel mobility shift, RNA footprinting in vitro

    PMID:17717080

    Open questions at the time
    • Identity of subsequently recruited subunits not determined
    • No atomic-resolution view of the RNA conformational change
  5. 2010 High

    Quantitative binding measurements and deletion mutagenesis pinpointed the Alba-type core domains as the minimal determinants for both heterodimerization and cooperative nM-affinity P3 RNA binding, definitively establishing cooperativity as the mechanism underlying RNA recognition.

    Evidence In vitro binding assays with deletion mutants, biophysical characterization

    PMID:20215441

    Open questions at the time
    • No structure of the RNA-bound complex
    • Contributions of regions outside the Alba core not fully resolved
  6. 2018 High

    The crystal structure of the free Rpp20–Rpp25 heterodimer revealed how quaternary-level divergence from archaeal Alba homodimers adapted the complex for single-stranded RNA recognition in the P3 internal loop.

    Evidence X-ray crystallography with comparative structural analysis

    PMID:29625199

    Open questions at the time
    • Structure lacked bound RNA, so the RNA-recognition interface was inferred rather than observed
  7. 2021 High

    The co-crystal structure of RPP20–RPP25 with the RMRP P3 domain provided the first atomic view of the protein–RNA interface, showing that a conserved positively charged surface contacts the distal stem and internal loop, and that cartilage-hair hypoplasia RMRP mutations cluster at this interface.

    Evidence X-ray crystallography of the ternary complex

    PMID:33571640

    Open questions at the time
    • Homodimeric organization of the ternary complex awaits validation in the context of the full holoenzyme
    • Functional impact of individual interface mutations not tested by mutagenesis-activity assays
  8. 2022 Medium

    Discovery that POP7 binds mRNA introns and stabilizes ILF3 mRNA to promote breast cancer progression expanded its functional repertoire beyond canonical RNase P/MRP activities.

    Evidence RIP-seq, mRNA stability assays, knockdown/overexpression with proliferation and invasion readouts in breast cancer cells and xenografts

    PMID:35579257

    Open questions at the time
    • Mechanism of mRNA stabilization not defined (direct vs. indirect)
    • Single-lab finding; not independently replicated
    • Relationship between RNase MRP function and mRNA stabilization role unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How POP7–Rpp25 heterodimer assembly integrates into full RNase P and RNase MRP holoenzyme architecture and catalytic mechanism in human cells remains unresolved, as does the physiological significance of the SMN interaction and the non-canonical mRNA-stabilizing activity.
  • No cryo-EM or crystal structure of the complete human RNase P or MRP holoenzyme with POP7 positioned
  • SMN interaction has no established functional consequence
  • mRNA stabilization mechanism and its relationship to canonical ribonuclease function are undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0005198 structural molecule activity 4
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-8953854 Metabolism of RNA 4
Partners
RPP25RPP30SMN1
Complex memberships
RNase MRPRNase P

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Pop6 and Pop7 (yeast orthologs of human Rpp25 and Rpp20) form a soluble heterodimer that binds the P3 domain of both RNase MRP and RNase P RNAs. Footprint analysis showed the Pop6/7 complex binds a conserved region of the P3 domain and induces local structural rearrangement of the P3 loop, suggesting it mediates binding of other protein components. Bacterial expression of recombinant proteins, gel mobility shift assays, RNA footprint analysis RNA (New York, N.Y.) High 17717080
1998 Rpp2 (yeast ortholog of human POP7/Rpp20) is a protein subunit of nuclear RNase P and RNase MRP; depletion of Rpp2 in vivo causes accumulation of precursor tRNAs with unprocessed introns and 5'/3' termini, and defects in processing of 35S precursor rRNA and 5.8S rRNA. Rpp2 immunoprecipitates cleave precursor tRNAs and rRNAs at expected sites and co-associate with the Rpp1 protein (ortholog of human Rpp30). Epitope-tagged immunoprecipitation, in vivo depletion, in vitro cleavage assay Proceedings of the National Academy of Sciences of the United States of America High 9618478
2006 Human Rpp20 (POP7 ortholog) and Rpp25 form a salt- and detergent-resistant heterodimer; heterodimerization strongly enhances their interaction with the P3 domain of RNase MRP RNA. Only a single copy of each protein associates with RNase MRP/P particles. Nucleolar accumulation of Rpp20 is strongly dependent on its interaction with Rpp25. Knockdown and overexpression experiments show their expression levels are codependent. Co-immunoprecipitation, gel filtration, RNA binding assays, immunofluorescence, knockdown/overexpression RNA (New York, N.Y.) High 17119099
2010 Human Rpp20 and Rpp25 individually bind the P3 arm of RNase MRP RNA with negligible affinity, but the 1:1 Rpp20:Rpp25 heterodimer binds the same target with nM affinity, establishing that heterodimer formation is a prerequisite for RNA recognition. Deletion analysis mapped the Alba-type core domain of both proteins as containing the key determinants for mutual association and P3 RNA binding. In vitro binding assays, biophysical characterization (CD, ITC/SPR implied), deletion mutagenesis Nucleic acids research High 20215441
2004 Human Rpp20 (POP7) interacts with SMN protein; the interaction was identified by yeast two-hybrid and validated by in vitro binding assays and co-immunoprecipitation. Exons 3-4 of SMN are necessary and sufficient for Rpp20 binding. In response to stress, SMN aggregates and redistributes Rpp20 from a diffuse nuclear/cytoplasmic distribution into punctuated cytoplasmic SMN granules. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation, immunofluorescence Biochemical and biophysical research communications Medium 14715275
2018 Crystal structure of the human Rpp20/Rpp25 (POP7/Rpp25) heterodimer was determined, revealing quaternary-level differences from archaeal Alba homodimers as the structural basis for adaptation to single-stranded RNA binding specificity in the P3 internal loop of RNase P/MRP. X-ray crystallography, comparative structural analysis Journal of molecular biology High 29625199
2021 Crystal structure of human RPP20-RPP25 (POP7-Rpp25) in complex with the P3 domain of lncRNA RMRP was determined; RPP20-RPP25 binds P3 RNA via a conserved positively-charged surface interacting with the distal stem and internal loop regions of P3. Disease-related RMRP mutations cluster at the protein-RNA interface. The structure also reveals a homodimeric organization of the entire RPP20-RPP25-RMRP P3 complex, suggesting dimerization of human RNase MRP complex in cells. X-ray crystallography Journal of structural biology High 33571640
2009 Crystals of a complex containing the P3 RNA domain of yeast RNase MRP with Pop6 and Pop7 proteins were obtained and diffracted to 3.25 Å, enabling structural analysis of how these proteins interact with the P3 RNA. X-ray crystallography (crystallization and preliminary diffraction) Acta crystallographica. Section F, Structural biology and crystallization communications Medium 20057077
2022 Human POP7 binds preferentially to intron regions of mRNAs (identified by RIP-seq) and promotes breast cancer progression by stabilizing ILF3 mRNA; knockdown of ILF3 impaired the malignant phenotypes conferred by POP7 overexpression, placing POP7 upstream of ILF3 in this pathway. RNA immunoprecipitation sequencing (RIP-seq), mRNA stability assay, knockdown/overexpression with functional readouts (proliferation, invasion, in vivo tumor growth) Cancer science Medium 35579257

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Functional analysis of the Asian soybean rust resistance pathway mediated by Rpp2. Molecular plant-microbe interactions : MPMI 47 20977308
2007 Specific binding of a Pop6/Pop7 heterodimer to the P3 stem of the yeast RNase MRP and RNase P RNAs. RNA (New York, N.Y.) 41 17717080
2006 Heterodimerization regulates RNase MRP/RNase P association, localization, and expression of Rpp20 and Rpp25. RNA (New York, N.Y.) 38 17119099
1998 Rpp2, an essential protein subunit of nuclear RNase P, is required for processing of precursor tRNAs and 35S precursor rRNA in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 37 9618478
2010 Heterodimerization of the human RNase P/MRP subunits Rpp20 and Rpp25 is a prerequisite for interaction with the P3 arm of RNase MRP RNA. Nucleic acids research 33 20215441
2004 Rpp20 interacts with SMN and is re-distributed into SMN granules in response to stress. Biochemical and biophysical research communications 29 14715275
2014 Fine mapping of the Asian soybean rust resistance gene Rpp2 from soybean PI 230970. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 20 25504467
2022 RNA binding protein POP7 regulates ILF3 mRNA stability and expression to promote breast cancer progression. Cancer science 10 35579257
2021 Crystal structure of human RPP20-RPP25 proteins in complex with the P3 domain of lncRNA RMRP. Journal of structural biology 10 33571640
2018 Crystal Structure of Human Rpp20/Rpp25 Reveals Quaternary Level Adaptation of the Alba Scaffold as Structural Basis for Single-stranded RNA Binding. Journal of molecular biology 9 29625199
2009 Crystallization and preliminary X-ray diffraction analysis of the P3 RNA domain of yeast ribonuclease MRP in a complex with RNase P/MRP protein components Pop6 and Pop7. Acta crystallographica. Section F, Structural biology and crystallization communications 6 20057077
2026 Rpp2 Encodes a TIR-NBS-WH-LRR Protein That Confers Resistance to Phakopsora pachyrhizi in Soybean. Molecular plant-microbe interactions : MPMI 0 41925523