LRPPRC (Leucine-rich PPR motif-containing protein) is a mitochondrial PPR protein that functions as a key regulator of mitochondrial mRNA metabolism. It forms a stable ribonucleoprotein complex with SLIRP (SRA stem-loop interacting RNA-binding protein) and performs three core functions: (1) stabilization of mitochondrial mRNAs by protecting them from 3'-5' exonucleolytic degradation by the PNPase/SUV3 degradosome, (2) promotion of polyadenylation of mt-mRNAs via MTPAP, and (3) delivery of mRNAs to the mitoribosome through direct interaction with mS39 and mS31. Cryo-EM structures (2024) reveal LRPPRC acts as an mRNA "holdase" that maintains proper mRNA folding for efficient translation. Loss of LRPPRC causes the French-Canadian form of Leigh syndrome (LSFC) with cytochrome c oxidase deficiency. While predominantly mitochondrial, a fraction localizes to the nucleus where it may participate in nuclear mRNA export via EIF4E.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0070129 regulation of mitochondrial translation | IBA GO_REF:0000033 | ACCEPT | Summary: LRPPRC regulates mitochondrial translation through its role in mRNA delivery to the mitoribosome. Cryo-EM studies (Singh et al., 2024) show LRPPRC-SLIRP docks on the small mitoribosomal subunit via mS39 and mS31, forming a corridor for mRNA delivery to the decoding center. Loss of LRPPRC causes transcript-specific translation efficiency changes, with COX1/COX2 translation reduced >2-fold while ND6 translation increases >2-fold (PMID:Singh et al. 2024). Reason: This annotation accurately captures a core function of LRPPRC. The IBA annotation is well-supported by extensive experimental evidence showing LRPPRC's role in delivering mRNAs to the mitoribosome and modulating translation efficiency in a transcript-specific manner. Supporting Evidence: file:human/LRPPRC/LRPPRC-deep-research-falcon.md Cryo-EM of human LRPPRC-SLIRP in complex with mRNA and the mitoribosome demonstrates direct association of LRPPRC with mS39 and mS31, with SLIRP directly holding mRNA; loss of LRPPRC yields transcript-specific translation efficiency (TE) changes PMID:22661577 In this article, we provide evidence that the LRPPRC/SLIRP complex suppresses mRNA degradation mediated by PNPase and SUV3 and promotes polyadenylation of mRNA mediated by mitochondrial poly(A) polymerase MTPAP in vitro |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: LRPPRC is predominantly localized to the mitochondrial matrix where it performs its core functions in mRNA metabolism. Multiple studies confirm mitochondrial localization via immunofluorescence, subcellular fractionation, and proteomics (PMID:12832482, PMID:34800366). Reason: Mitochondrial localization is a core aspect of LRPPRC function and is extensively validated by multiple experimental approaches. UniProt notes "Seems to be predominantly mitochondrial." Supporting Evidence: PMID:12832482 The majority of LRP130 proteins are located within mitochondria, where they are directly bound to polyadenylated RNAs in vivo |
| GO:0003730 mRNA 3'-UTR binding | IBA GO_REF:0000033 | MODIFY | Summary: LRPPRC binds mitochondrial mRNAs; however, mitochondrial mRNAs lack classical 3'-UTRs. LRPPRC-SLIRP binds primarily to coding sequences of mt-mRNAs rather than UTR regions. The 3'-UTR binding annotation may be more appropriate for nuclear RNA interactions or reflect ortholog functions in other species. Reason: While LRPPRC does bind mRNA, the specific term "mRNA 3'-UTR binding" is misleading for its primary mitochondrial function where it binds coding sequences. A more appropriate term would be "mRNA binding" (GO:0003729) which is already annotated with IDA evidence. Proposed replacements: mRNA binding Supporting Evidence: PMID:22661577 The LRPPRC/SLIRP complex recognizes mRNA coding sequences PMID:12832482 In vitro, LRP130 binds preferentially to polypyrimidines. This RNA-binding activity maps to a domain in its C-terminal region |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A fraction of LRPPRC localizes to the nucleus where it participates in mRNA export via interaction with EIF4E and XPO1/CRM1. Multiple IDA studies confirm nuclear localization (PMID:12762840, PMID:12832482). Reason: Nuclear localization is real but represents a secondary function. The primary function of LRPPRC is in the mitochondrial matrix. Nuclear localization relates to its proposed role in mRNA export which is less well-established than its mitochondrial functions. Supporting Evidence: PMID:12832482 We show here that only a fraction of LRP130 proteins are in nuclei and are directly bound in vivo to at least some of the same RNA molecules as the nucleocytoplasmic shuttle protein hnRNP A1 |
| GO:0003677 DNA binding | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: This annotation derives from UniProt keyword mapping. UniProt states LRPPRC "Binds single-stranded DNA (By similarity)." However, there is no direct experimental evidence for DNA binding by human LRPPRC. The core function is RNA binding, not DNA binding. Reason: DNA binding is inferred by similarity and not experimentally demonstrated for human LRPPRC. The protein's established functions are all related to RNA metabolism. This annotation should be deprioritized as it does not reflect a core or well-established function. Supporting Evidence: PMID:12832482 LRP130 is a novel type of RNA-binding protein that associates with both nuclear and mitochondrial mRNAs |
| GO:0003723 RNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: RNA binding is a core function of LRPPRC, extensively validated by multiple experimental approaches. LRPPRC binds both mitochondrial and nuclear mRNAs. This IEA annotation duplicates well-supported HDA annotations from PMID:22658674 and PMID:22681889. Reason: RNA binding is a fundamental molecular function of LRPPRC. Even though this is an IEA annotation, it is correct and supported by extensive experimental evidence. Supporting Evidence: PMID:12832482 LRP130 is a novel type of RNA-binding protein that associates with both nuclear and mitochondrial mRNAs |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Duplicate of IBA annotation. Nuclear localization is supported but represents a minor fraction of LRPPRC protein. Reason: Valid but non-core localization. The majority of LRPPRC is mitochondrial. Supporting Evidence: PMID:12832482 only a fraction of LRP130 proteins are in nuclei |
| GO:0005637 nuclear inner membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: This annotation derives from UniProt subcellular location mapping. UniProt lists "Nucleus inner membrane" but the evidence for this specific localization is limited. Reason: While LRPPRC has nuclear localization, specific localization to the nuclear inner membrane is not well-supported by experimental evidence. This appears to be an over-specific inference from general nuclear localization data. |
| GO:0005640 nuclear outer membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: This annotation derives from UniProt subcellular location mapping. One study (PMID:15081402) suggested outer nuclear membrane localization, but this is not the primary or well-established localization. Reason: Nuclear outer membrane localization is mentioned in early literature but not confirmed by more recent comprehensive studies. The primary localization is mitochondrial matrix. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: LRPPRC has been detected in the nucleus but specific nucleoplasmic localization versus other nuclear compartments is not well-established. Reason: Nuclear localization is documented, and nucleoplasm is a reasonable inference for the nuclear fraction. Kept as non-core since mitochondrial localization is primary. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. Mitochondrial localization is the primary and best-supported localization for LRPPRC. Reason: This is the core localization for LRPPRC function. Duplicates are acceptable when supported by multiple evidence types. Supporting Evidence: PMID:12832482 The majority of LRP130 proteins are located within mitochondria |
| GO:0006914 autophagy | IEA GO_REF:0000043 | REMOVE | Summary: This annotation derives from UniProt keyword mapping based on PMID:23822101 which reported LRPPRC suppresses basal autophagy via BCL2 stabilization. However, this is likely a secondary consequence of mitochondrial dysfunction rather than a direct function of LRPPRC. The primary role of LRPPRC is in mitochondrial mRNA metabolism, not autophagy regulation. Reason: This is an OVER-ANNOTATION. LRPPRC's core function is in mitochondrial mRNA metabolism. The reported autophagy suppression (via BCL2/BECN1 interaction) is likely an indirect effect or artifact of its role in maintaining mitochondrial function. When mitochondria are dysfunctional due to LRPPRC deficiency, mitophagy may be triggered as a secondary response. The protein does not function as an autophagy regulator per se. |
| GO:0051028 mRNA transport | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: This annotation derives from UniProt keyword mapping. LRPPRC has been implicated in nuclear mRNA export via EIF4E interactions (PMID:19262567, PMID:28325843). However, this is a secondary function compared to its mitochondrial role. Reason: mRNA transport/export is supported by literature but represents a minor function compared to the well-established mitochondrial mRNA metabolism role. The nuclear mRNA export function involves only a fraction of LRPPRC protein. Supporting Evidence: PMID:19262567 This protein associates with mRNAs containing the eIF4E-sensitivity element (4E-SE), and its overexpression alters the nuclear export of several eIF4E-sensitive mRNAs |
| GO:0005515 protein binding | IPI PMID:15161933 Comprehensive proteomic analysis of interphase and mitotic 1... | MODIFY | Summary: This annotation captures LRPPRC interaction with 14-3-3 proteins (specifically YWHAZ). The interaction was identified in a proteomic screen for 14-3-3 binding proteins. Reason: "Protein binding" is uninformative. The actual interaction is with 14-3-3 proteins. Should be replaced with a more specific term if available, or kept but noted as non-core. The biological significance of this interaction is unclear. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:15161933 14-3-3-binding proteins were purified from extracts of interphase and mitotic HeLa cells |
| GO:0005515 protein binding | IPI PMID:17050673 Defects in energy homeostasis in Leigh syndrome French Canad... | MODIFY | Summary: This annotation captures LRPPRC interaction with PPARGC1A (PGC-1alpha). This interaction is relevant to energy homeostasis and gluconeogenic gene regulation and is documented in the context of Leigh syndrome French Canadian variant. Reason: The interaction with PGC-1alpha is biologically significant but "protein binding" is uninformative. The specific interactor is a transcriptional coactivator. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:17050673 Oct 18. Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complex. |
| GO:0005515 protein binding | IPI PMID:17314511 Large-scale identification of c-MYC-associated proteins usin... | KEEP AS NON CORE | Summary: This annotation captures LRPPRC interaction with c-MYC (P01106), identified in a large-scale TAP/MudPIT study. Reason: High-throughput interaction data; biological significance unclear. The term "protein binding" is uninformative but there is no more specific term available. Supporting Evidence: PMID:17314511 Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach. |
| GO:0005515 protein binding | IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by... | KEEP AS NON CORE | Summary: Large-scale protein-protein interaction mapping study. LRPPRC interactions with P01106 (MYC) and Q9Y2Q3 (GAB1) were identified. Reason: High-throughput data with unclear biological significance for LRPPRC function. Supporting Evidence: PMID:17353931 Large-scale mapping of human protein-protein interactions by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:19262567 Molecular dissection of the eukaryotic initiation factor 4E ... | MODIFY | Summary: This annotation captures LRPPRC interaction with EIF4E. This is a functionally significant interaction related to nuclear mRNA export. LRPPRC binds simultaneously to EIF4E and 4ESE-containing mRNAs to promote mRNA export. Reason: This is a biologically meaningful interaction but "protein binding" is uninformative. EIF4E binding is relevant to the nuclear mRNA export function of LRPPRC. Proposed replacements: eukaryotic initiation factor 4E binding Supporting Evidence: PMID:19262567 we identified candidate cofactors of eIF4E mRNA export including LRPPRC |
| GO:0005515 protein binding | IPI PMID:21150319 Proteomic profiling of Myc-associated proteins. | KEEP AS NON CORE | Summary: Proteomic profiling of Myc-associated proteins. LRPPRC interaction with MYC identified. Reason: High-throughput data; biological significance for LRPPRC core function unclear. Supporting Evidence: PMID:21150319 Dec 15. Proteomic profiling of Myc-associated proteins. |
| GO:0005515 protein binding | IPI PMID:22045337 LRPPRC is necessary for polyadenylation and coordination of ... | MODIFY | Summary: This annotation captures LRPPRC interaction with SLIRP (Q9GZT3). This is the most functionally significant protein interaction for LRPPRC - SLIRP and LRPPRC form a stable RNP complex essential for mitochondrial mRNA metabolism. Reason: The LRPPRC-SLIRP interaction is THE core functional interaction. "Protein binding" fails to capture its significance. These proteins are mutually stabilizing and function as an obligate complex. Proposed replacements: molecular condensate scaffold activity Supporting Evidence: PMID:22661577 the LRPPRC/SLIRP complex suppresses mRNA degradation mediated by PNPase and SUV3 and promotes polyadenylation of mRNA PMID:22045337 LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. |
| GO:0005515 protein binding | IPI PMID:25959826 Quantitative interaction proteomics of neurodegenerative dis... | KEEP AS NON CORE | Summary: Interaction with APP (amyloid precursor protein) identified in neurodegenerative disease protein interaction study. Reason: High-throughput interaction data; relevance to LRPPRC core function unclear. Supporting Evidence: PMID:25959826 2015 May 7. Quantitative interaction proteomics of neurodegenerative disease proteins. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | ACCEPT | Summary: Another study confirming LRPPRC-SLIRP interaction in a quantitative interactome study. Reason: Confirms the core LRPPRC-SLIRP interaction, though "protein binding" remains uninformative. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | ACCEPT | Summary: Dual proteome-scale network study confirming LRPPRC-SLIRP interaction. Reason: Additional confirmation of core LRPPRC-SLIRP interaction. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | KEEP AS NON CORE | Summary: Study on 14-3-3 proteins; confirms LRPPRC interaction with 14-3-3 (YWHAZ). Reason: 14-3-3 binding is documented but biological significance for LRPPRC function unclear. Supporting Evidence: PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human cells. |
| GO:0003697 single-stranded DNA binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This annotation is transferred from mouse ortholog. While UniProt states LRPPRC "Binds single-stranded DNA (By similarity)", this is not a well-established function for human LRPPRC. The primary binding function is to RNA. Reason: No direct experimental evidence for ssDNA binding by human LRPPRC. The protein's core function is RNA binding in mitochondria. DNA binding annotation should be deprioritized. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: LRPPRC is present in cytoplasm, consistent with its mitochondrial localization and potential cytoskeletal interactions. Reason: Cytoplasm is a broad term that encompasses mitochondria. This annotation is technically correct though less informative than the more specific mitochondrion annotation. |
| GO:1990904 ribonucleoprotein complex | IEA GO_REF:0000107 | ACCEPT | Summary: LRPPRC forms a stable RNP complex with SLIRP and mitochondrial mRNAs. This is central to its function. Reason: The LRPPRC-SLIRP-mRNA complex is well-established and central to LRPPRC function. Supporting Evidence: PMID:22661577 which we find that cotranscriptionally binds to coding sequences of mRNAs |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: IDA annotation based on immunofluorescence data (Human Protein Atlas). Confirms mitochondrial localization. Reason: Core localization confirmed by immunofluorescence. Consistent with other evidence. |
| GO:0003729 mRNA binding | IDA PMID:22661577 LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promo... | ACCEPT | Summary: LRPPRC binds mitochondrial mRNAs as demonstrated by RNA immunoprecipitation and other biochemical approaches. This is a core molecular function. Reason: mRNA binding is a well-established core function of LRPPRC, essential for its role in mRNA stabilization and delivery to the mitoribosome. Supporting Evidence: PMID:22661577 which we find that cotranscriptionally binds to coding sequences of mRNAs PMID:12832482 they are directly bound to polyadenylated RNAs in vivo |
| GO:0097222 mitochondrial mRNA polyadenylation | IDA PMID:22661577 LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promo... | ACCEPT | Summary: LRPPRC promotes polyadenylation of mitochondrial mRNAs via MTPAP. In vitro assays demonstrate LRPPRC enhances MTPAP-mediated polyadenylation. Reason: This is a core function of LRPPRC. The study provides direct experimental evidence that LRPPRC promotes MTPAP-mediated polyadenylation of mt-mRNAs. Supporting Evidence: PMID:22661577 LRPPRC promoted the polyadenylation of mRNAs mediated by mitochondrial poly(A) polymerase (MTPAP) in vitro |
| GO:1905638 negative regulation of mitochondrial mRNA catabolic process | IMP PMID:22661577 LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promo... | ACCEPT | Summary: LRPPRC/SLIRP complex suppresses 3'-5' exonucleolytic degradation of mt-mRNAs by PNPase and SUV3. Knockdown of LRPPRC/SLIRP leads to accelerated mRNA decay. Reason: This is a core function of LRPPRC. The mutant phenotype (accelerated mRNA decay upon knockdown) provides direct evidence for this regulatory function. Supporting Evidence: PMID:22661577 the LRPPRC/SLIRP complex suppressed 3' exonucleolytic mRNA degradation mediated by PNPase and SUV3 PMID:22661577 Taken together with the accelerated decay of several mRNAs upon SLIRP knock down (Figure 2A), the results suggest that the LRPPRC/SLIRP complex stabilizes a set of mRNAs by suppressing 3′–5′ exonuclease activity performed by PNPase and SUV3 |
| GO:0005759 mitochondrial matrix | IDA PMID:23275553 Alternative translation initiation augments the human mitoch... | ACCEPT | Summary: LRPPRC localizes to the mitochondrial matrix where it performs its mRNA metabolism functions. This is more specific than general mitochondrion annotation. Reason: Mitochondrial matrix is the specific sub-compartment where LRPPRC functions in mRNA stabilization, polyadenylation, and delivery to the mitoribosome. The cryo-EM study of the LRPPRC-SLIRP-mitoribosome assembly (DOI:10.1038/s41594-024-01365-9) is consistent with a matrix location, but that paper does not itself state the sub-compartment, so no quotation from it is cited here. PMID:23275553 was also attached to this row; its supporting_text was that paper's title with a scraped journal date in front of it, and LRPPRC appears in that paper only as an antibody in a methods list, so it is no evidence for a matrix localization. That citation has been removed too. The annotation stands on the GOA evidence in its own right. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput quantitative mitochondrial proteome study confirms LRPPRC as a mitochondrial protein. Reason: Additional confirmation of core localization from high-quality proteomics study. Supporting Evidence: PMID:34800366 Epub 2021 Nov 19. Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | KEEP AS NON CORE | Summary: LRPPRC interacts with Parkin (O60260), an E3 ubiquitin ligase. Study examined Parkin interactors in context of mitochondrial function. Reason: The interaction with Parkin is documented but its biological significance for LRPPRC function is unclear. May relate to mitochondrial quality control but is not a core LRPPRC function. Supporting Evidence: PMID:19725078 Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Membrane proteome study of NK cells identified LRPPRC. The annotation is very general and less informative than more specific localizations. Reason: This is a very general annotation. LRPPRC is primarily a soluble matrix protein, though it may associate with membranes in some contexts. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9837034 | ACCEPT | Summary: Reactome pathway "SLIRP:LRPPRC binds mitochondrial RNAs" places the complex in the mitochondrial matrix. Reason: Consistent with other evidence for mitochondrial matrix localization. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: Atlas of mammalian mRNA-binding proteins identifies LRPPRC as an RNA-binding protein through oligo(dT) capture and mass spectrometry. Reason: RNA binding is a core function of LRPPRC, confirmed by this systematic study. Supporting Evidence: PMID:22658674 May 31. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: mRNA-bound proteome study confirms LRPPRC as an RNA-binding protein. Reason: Additional confirmation of core RNA-binding function. Supporting Evidence: PMID:22681889 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. |
| GO:0005874 microtubule | IDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ... | KEEP AS NON CORE | Summary: Study on peroxisome motility found LRPPRC associated with microtubules. This relates to proposed cytoskeletal interactions. Reason: Microtubule association has been reported but is not the primary localization or function of LRPPRC. May be related to mitochondrial transport along microtubules but is not a core function. Supporting Evidence: PMID:21525035 Apr 26. PEX14 is required for microtubule-based peroxisome motility in human cells. |
| GO:0042645 mitochondrial nucleoid | IDA PMID:18063578 The layered structure of human mitochondrial DNA nucleoids. | KEEP AS NON CORE | Summary: LRPPRC was identified in the mitochondrial nucleoid, the structure containing mtDNA and associated proteins. This localization is consistent with roles in mitochondrial gene expression. Reason: Nucleoid localization is documented but LRPPRC's primary function is in mRNA metabolism rather than DNA-related processes. Nucleoid association may reflect physical proximity rather than functional involvement. Supporting Evidence: PMID:18063578 2007 Dec 6. The layered structure of human mitochondrial DNA nucleoids. |
| GO:0005634 nucleus | IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ... | KEEP AS NON CORE | Summary: Nuclear localization demonstrated by immunofluorescence and GFP-tagging in cultured cells. Reason: Nuclear localization is documented but represents a minor fraction of total cellular LRPPRC. The majority is mitochondrial. Supporting Evidence: PMID:12762840 LRPPRC appears in both cytosol and nuclei of cultured cells |
| GO:0048487 beta-tubulin binding | IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ... | KEEP AS NON CORE | Summary: Study reported LRPPRC colocalization with beta-tubulin and suggested direct interaction. However, this is not the primary function. Reason: Beta-tubulin binding/colocalization was reported in early studies but is not the core function of LRPPRC. The primary function is mitochondrial mRNA metabolism. Cytoskeletal interactions may be related to mitochondrial transport but are secondary. Supporting Evidence: PMID:12762840 colocalizes with mitochondria and beta-tubulin rather than with alpha-actin in the cytosol |
| GO:0051015 actin filament binding | IDA NOT PMID:12762840 Novel complex integrating mitochondria and the microtubular ... | ACCEPT | Summary: The study explicitly showed LRPPRC does NOT colocalize with actin filaments. This is a negated annotation (NOT actin filament binding). Reason: Negated annotations are valuable. The study specifically tested and excluded actin filament binding/colocalization. Supporting Evidence: PMID:12762840 colocalizes with mitochondria and beta-tubulin rather than with alpha-actin |
| GO:0000794 condensed nuclear chromosome | IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ... | KEEP AS NON CORE | Summary: Study showed LRPPRC association with condensed chromosomes during mitosis. GFP-tagged CECR2B colocalized with condensed DNA. LRPPRC showed phase-dependent organization around separating chromosomes. Reason: This observation relates to potential nuclear functions during mitosis but is not a core LRPPRC function. The primary function is mitochondrial. Supporting Evidence: PMID:12762840 exhibits phase-dependent organization around separating chromosomes in mitotic cells |
| GO:0005739 mitochondrion | IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ... | ACCEPT | Summary: Early study demonstrating mitochondrial colocalization of LRPPRC. Reason: Core localization confirmed by multiple approaches. Supporting Evidence: PMID:12762840 colocalizes with mitochondria and beta-tubulin |
| GO:0005856 cytoskeleton | IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ... | KEEP AS NON CORE | Summary: LRPPRC was reported to colocalize with cytoskeletal elements, specifically beta-tubulin but not actin. Reason: Cytoskeletal association is documented but is not the primary localization or function. May relate to mitochondrial transport but is secondary to the matrix-localized mRNA metabolism function. Supporting Evidence: PMID:12762840 Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells. |
| GO:0008017 microtubule binding | TAS PMID:12762840 Novel complex integrating mitochondria and the microtubular ... | KEEP AS NON CORE | Summary: TAS annotation based on colocalization studies showing LRPPRC association with microtubules/beta-tubulin. Reason: Microtubule binding/association is documented but is not the core molecular function. The primary function is RNA binding in mitochondrial mRNA metabolism. Supporting Evidence: PMID:12762840 Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells. |
| GO:0047497 mitochondrion transport along microtubule | TAS PMID:12762840 Novel complex integrating mitochondria and the microtubular ... | MARK AS OVER ANNOTATED | Summary: Annotation suggests LRPPRC involvement in mitochondrial transport along microtubules, based on proposed complex linking mitochondria to cytoskeleton. Reason: While the study proposed a role in linking mitochondria to microtubules, subsequent work has not validated this as a primary function. The well- established functions are in mitochondrial mRNA metabolism. This annotation may over-represent an unconfirmed hypothesis. Supporting Evidence: PMID:12762840 Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ... | KEEP AS NON CORE | Summary: LRPPRC was observed in the perinuclear region, consistent with mitochondrial localization as mitochondria often cluster in this region. Reason: Perinuclear localization is consistent with mitochondrial distribution but is less informative than the specific mitochondrial matrix annotation. Supporting Evidence: PMID:12762840 Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells. |
| GO:0005515 protein binding | IPI PMID:15907802 Putative tumor suppressor RASSF1 interactive protein and cel... | KEEP AS NON CORE | Summary: Study on MAP1S (C19ORF5) identified its interaction with LRPPRC. MAP1S was proposed as part of a complex linking mitochondria to cytoskeleton. Reason: Interaction is documented but biological significance for LRPPRC core function is unclear. Supporting Evidence: PMID:15907802 Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein. |
| GO:0003723 RNA binding | NAS PMID:12832482 LRP130, a pentatricopeptide motif protein with a noncanonica... | ACCEPT | Summary: Non-traceable author statement supporting RNA binding function based on the landmark Mili & Pinol-Roma 2003 study. Reason: RNA binding is a core function, extensively validated by this and other studies. Supporting Evidence: PMID:12832482 LRP130 is a novel type of RNA-binding protein that associates with both nuclear and mitochondrial mRNAs |
| GO:0005634 nucleus | IDA PMID:12832482 LRP130, a pentatricopeptide motif protein with a noncanonica... | KEEP AS NON CORE | Summary: IDA evidence for nuclear localization from the 2003 study that characterized LRPPRC as binding both nuclear and mitochondrial RNAs. Reason: Nuclear localization is documented for a fraction of LRPPRC. The study showed most LRPPRC is mitochondrial but some is nuclear. Supporting Evidence: PMID:12832482 only a fraction of LRP130 proteins are in nuclei |
| GO:0005739 mitochondrion | IDA PMID:12832482 LRP130, a pentatricopeptide motif protein with a noncanonica... | ACCEPT | Summary: Key study demonstrating predominant mitochondrial localization of LRPPRC. Reason: This is the core localization for LRPPRC function. Supporting Evidence: PMID:12832482 The majority of LRP130 proteins are located within mitochondria, where they are directly bound to polyadenylated RNAs in vivo |
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Download this section (compressed HTML)Q: Is the nuclear mRNA export function of LRPPRC biologically significant or a minor moonlighting activity?
Q: What is the molecular basis for transcript-specific effects on translation efficiency?
Q: How does LRPPRC recognize its mRNA substrates without sequence-specific binding motifs?
Experiment: CLIP-seq to map LRPPRC binding sites on mt-mRNAs at nucleotide resolution
Experiment: Structure-function analysis of LRPPRC-mS39/mS31 interaction interface
Experiment: Time-resolved analysis of mRNA delivery from LRPPRC-SLIRP to active ribosomes
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