A1CF (APOBEC1 complementation factor) is a three-RRM, nucleocytoplasmic RNA-binding protein that recognizes sequence-defined single-stranded RNA elements and regulates tissue-selective alternative splicing, including metabolic transcripts in hepatocytes and pancreatic beta cells. A1CF can also bind APOB RNA and recruit the catalytic deaminase APOBEC1 within an APOB mRNA-editing complex, but this contribution is tissue- and substrate-dependent and partly redundant with RBM47 rather than universally required. A1CF-containing editosomes can protect edited APOB RNA from nonsense-mediated decay; in mouse Kupffer cells, A1cf also stabilizes IL6 mRNA after partial hepatectomy. A1CF shuttles between the nucleoplasm and cytoplasm through a TNPO2-recognized nuclear-targeting sequence.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003729 mRNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: A1CF directly binds APOB mRNA, including the editing-site region. Reason: Direct UV-crosslinking supports mRNA binding as a central A1CF activity. Supporting Evidence: PMID:10669759 By UV cross-linking and immunoprecipitation, we show that ACF binds to apo-B mRNA in vitro and in vivo. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: A1CF localizes to the nucleus and undergoes nucleocytoplasmic shuttling. Reason: Direct localization experiments support nuclear activity. Supporting Evidence: PMID:12896982 ACF expression is predominantly nuclear, including mutant proteins with deletions of a putative nuclear localization signal. |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: Nucleic acid binding is true but too broad for this sequence-specific mRNA-binding protein. Reason: Replace the generic InterPro-derived term with the experimentally demonstrated sequence-specific mRNA-binding activity. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:11871661 This complex contains apobec-1, the catalytic subunit, and apobec-1 complementation factor (ACF), the RNA-binding subunit that binds to the mooring sequence. |
| GO:0003723 RNA binding | IEA GO_REF:0000120 | MODIFY | Summary: RNA binding is supported, but single-stranded RNA is the relevant substrate class. Reason: The direct binding assay supports the more precise single-stranded RNA-binding term. Proposed replacements: single-stranded RNA binding Supporting Evidence: PMID:11871661 Here, we show that ACF binds with high affinity to single-stranded but not double-stranded apo-B mRNA. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: A1CF is a nuclear protein that also shuttles to the cytoplasm. Reason: The automated localization is independently supported by direct experiment. Supporting Evidence: PMID:12896982 ACF expression is predominantly nuclear, including mutant proteins with deletions of a putative nuclear localization signal. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: A1CF also occupies the cytoplasm during its shuttling cycle. Reason: Microscopy and fractionation directly show cytoplasmic A1CF. Supporting Evidence: PMID:12881431 In the absence of APOBEC1, we found ACF to localize predominantly to the cytoplasm, with some nuclear localization. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A minor A1CF pool associates with rough endoplasmic-reticulum membranes. Reason: This human annotation is inferred by similarity and reflects a secondary edited-RNA transport stage. ORGANELLES check (2026-11-04): the IEA maps the UniProt line "Endoplasmic reticulum {ECO:0000250}", whose basis is rodent work (the note places A1CF at the outer surface of the ER, by similarity). The cached full text of PMID:12881431 cites ultrastructural analysis in rodent liver showing endogenous ACF mainly nuclear and to a lesser extent on rough ER membranes, where the APOBEC1-ACF complex is proposed to deliver edited apoB mRNA for translation. The organelle claim holds as a minor cytoplasmic pool, so the row stays KEEP_AS_NON_CORE. No sub-compartment is added: A1CF is a soluble RNA-binding protein with no signal peptide or membrane segment, so it is bound to the cytosolic face of the ER and is neither in the ER membrane nor in the lumen; as with recruited surface pools on mitochondria, the row stays at the root. Supporting Evidence: PMID:12881431 These findings are supported by the recent ultrastructural analysis of Sowden et al. (2002) , which showed that in rodent liver cells expressing endogenous APOBEC1 and ACF, ACF is mainly in the nucleus and to a lesser extent localized to the membranes of the rough endoplasmic reticulum (ER). PMID:12881431 These results together suggest that the APOBEC1–ACF complex transports the edited apoB mRNA from the nucleus to the ER for translation. file:human/A1CF/A1CF-uniprot.txt Also cytoplasmic where it is found at the outer surface of the endoplasmic reticulum (By similarity). |
| GO:0030895 apolipoprotein B mRNA editing enzyme complex | IEA GO_REF:0000117 | ACCEPT | Summary: A1CF is a noncatalytic component of APOBEC1-containing APOB mRNA-editing complexes. Reason: Biochemical isolation and co-immunoprecipitation support complex membership; RBM47 provides overlapping cofactor function. Supporting Evidence: PMID:10669759 Coimmunoprecipitation experiments identified an ACF-apobec-1 complex in transfected cells. |
| GO:0140767 enzyme-substrate adaptor activity | IEA GO_REF:0000117 | ACCEPT | Summary: A1CF binds APOB mRNA and recruits catalytic APOBEC1 to its target cytidine. Reason: The direct docking model fits enzyme-substrate adaptor activity; A1CF is not the deaminase. Supporting Evidence: PMID:10669759 Our results support a model of the editing enzyme in which ACF binds to the mooring sequence in apo-B mRNA and docks apobec-1 to deaminate its target cytidine. |
| GO:1902373 negative regulation of mRNA catabolic process | IEA GO_REF:0000117 | MODIFY | Summary: A1CF-containing editosomes protect edited premature-stop-containing mRNA from nonsense-mediated decay. Reason: The automated process is too broad; the experiments support the specific NMD-regulatory term. Proposed replacements: negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Supporting Evidence: PMID:12881431 The APOBEC1-ACF complex edits and remains associated with the edited RNA to protect it from NMD. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: A1CF was recovered with REL, TRAF1, and FHL3 in a proteome-scale binary-interaction screen. Reason: The contacts lack mechanistic A1CF context, and generic protein binding is not an informative function. Supporting Evidence: PMID:25416956 Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: A1CF has multiple binary-interaction hits in the HuRI reference map. Reason: High-throughput contacts do not establish a specific A1CF molecular activity; generic protein binding is uninformative. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0016554 cytidine to uridine editing | IEA GO_REF:0000120 | ACCEPT | Summary: A1CF can participate as a noncatalytic cofactor in APOBEC1-dependent C-to-U RNA editing. Reason: Human assays support editing, while mouse genetics shows a redundant, tissue-specific contribution rather than universal necessity. Supporting Evidence: PMID:30844405 A1CF showed a transition from cytosine to uracil on 56% of the observed sequences, whereas RBM47 showed conversion on 75%. PMID:30309881 These data suggest that A1CF and RBM47 each function independently, yet interact in a tissue-specific manner, to regulate the activity and site selection of APOBEC1 dependent C-to-U RNA editing. |
| GO:0005634 nucleus | IDA PMID:12881431 The apolipoprotein B mRNA editing complex performs a multifu... | ACCEPT | Summary: A1CF localizes to the nucleus during its APOBEC1-associated editing cycle. Reason: The cited full text directly reports nuclear localization under APOBEC1 coexpression. Supporting Evidence: PMID:12881431 Co-expression of APOBEC1 and ACF localized both proteins to the nucleus. |
| GO:0016556 mRNA modification | IDA PMID:11134005 Identification of GRY-RBP as an apolipoprotein B RNA-binding... | MODIFY | Summary: The cited study concerns C-to-U modification of APOB mRNA. Reason: Generic mRNA modification is less informative than the specific editing process. Proposed replacements: cytidine to uridine editing Supporting Evidence: PMID:11134005 This enzyme complex includes apobec-1, an RNA-specific cytidine deaminase, and apobec-1 complementation factor (ACF), a novel 65-kDa RNA-binding protein, that together represent the minimal core of the editing enzyme complex. |
| GO:0045293 mRNA editing complex | NAS PMID:11134005 Identification of GRY-RBP as an apolipoprotein B RNA-binding... | MODIFY | Summary: A1CF belongs specifically to the APOB mRNA editing enzyme complex. Reason: The paper supports the APOB-specific complex rather than an unspecified mRNA-editing complex. Proposed replacements: apolipoprotein B mRNA editing enzyme complex Supporting Evidence: PMID:11134005 This enzyme complex includes apobec-1, an RNA-specific cytidine deaminase, and apobec-1 complementation factor (ACF), a novel 65-kDa RNA-binding protein, that together represent the minimal core of the editing enzyme complex. |
| GO:0141166 chromosomal 5-methylcytosine DNA demethylation pathway | NAS PMID:21496894 Hydroxylation of 5-methylcytosine by TET1 promotes active DN... | UNDECIDED | Summary: The cited paper supports TET1- and APOBEC1-associated DNA demethylation but exposes no A1CF experiment. Reason: This NAS assertion may be propagated from APOBEC1 complex membership; direct A1CF participation cannot be verified. Supporting Evidence: PMID:21496894 Furthermore, Tet1 and Apobec1 are involved in neuronal activity-induced, region-specific, active DNA demethylation and subsequent gene expression in the dentate gyrus of the adult mouse brain in vivo. |
| GO:2000623 negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay | IDA PMID:12881431 The apolipoprotein B mRNA editing complex performs a multifu... | KEEP AS NON CORE | Summary: A1CF-containing APOB editosomes can shield edited transcripts from nonsense-mediated decay. Reason: The effect is supported but is a substrate- and complex-dependent consequence of editing, not A1CF's primary activity. Supporting Evidence: PMID:12881431 The association of the APOBEC1–ACF complex with the bona fide edited RNA is essential to protect it from undergoing NMD. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence places A1CF in the nucleoplasm, consistent with established nuclear localization. Reason: The HPA call is concordant with direct localization and shuttling studies. Supporting Evidence: PMID:12896982 ACF expression is predominantly nuclear, including mutant proteins with deletions of a putative nuclear localization signal. |
| GO:0140767 enzyme-substrate adaptor activity | IDA PMID:11871661 Identification of domains in apobec-1 complementation factor... | ACCEPT | Summary: A1CF binds APOB RNA and helps position APOBEC1 for deamination. Reason: Domain and docking experiments support enzyme-substrate adaptor activity. Supporting Evidence: PMID:10669759 Our results support a model of the editing enzyme in which ACF binds to the mooring sequence in apo-B mRNA and docks apobec-1 to deaminate its target cytidine. |
| GO:0140767 enzyme-substrate adaptor activity | IDA PMID:24916387 C to U RNA editing mediated by APOBEC1 requires RNA-binding ... | ACCEPT | Summary: A1CF can function as an APOBEC1 enzyme-substrate adaptor. Reason: The docking mechanism is established, but RBM47 is often dominant in vivo and A1CF is context-dependent. Supporting Evidence: PMID:10669759 Our results support a model of the editing enzyme in which ACF binds to the mooring sequence in apo-B mRNA and docks apobec-1 to deaminate its target cytidine. PMID:30309881 These data suggest that A1CF and RBM47 each function independently, yet interact in a tissue-specific manner, to regulate the activity and site selection of APOBEC1 dependent C-to-U RNA editing. |
| GO:0016554 cytidine to uridine editing | IDA PMID:30844405 Comparison of RNA Editing Activity of APOBEC1-A1CF and APOBE... | ACCEPT | Summary: Human A1CF supports APOBEC1-dependent C-to-U editing in a reconstituted cell system. Reason: Direct human data support participation; mouse genetics shows redundancy and tissue specificity. Supporting Evidence: PMID:30844405 A1CF showed a transition from cytosine to uracil on 56% of the observed sequences, whereas RBM47 showed conversion on 75%. PMID:28069890 Taken together, these observations demonstrate that A1CF does not act as the APOBEC1 complementation factor in vivo under normal physiological conditions and suggests new roles for A1CF, specifically within the male adult kidney. PMID:30309881 These data suggest that A1CF and RBM47 each function independently, yet interact in a tissue-specific manner, to regulate the activity and site selection of APOBEC1 dependent C-to-U RNA editing. |
| GO:0030895 apolipoprotein B mRNA editing enzyme complex | IDA PMID:24916387 C to U RNA editing mediated by APOBEC1 requires RNA-binding ... | ACCEPT | Summary: A1CF participates in APOBEC1-containing editing complexes and can interact with RBM47. Reason: The cited study places A1CF in the editing-cofactor network, and independent co-IP establishes the APOBEC1 complex. Supporting Evidence: PMID:24916387 We identify and characterise here a novel RNA-binding protein, RBM47, that interacts with APOBEC1 and A1CF and is expressed in tissues where C to U RNA editing occurs. PMID:10669759 Coimmunoprecipitation experiments identified an ACF-apobec-1 complex in transfected cells. |
| GO:0005515 protein binding | IPI PMID:24916387 C to U RNA editing mediated by APOBEC1 requires RNA-binding ... | MARK AS OVER ANNOTATED | Summary: The cited study supports an A1CF-RBM47 interaction in the RNA-editing cofactor network. Reason: The interaction is credible, but generic protein binding omits the editing-complex context. Supporting Evidence: PMID:24916387 We identify and characterise here a novel RNA-binding protein, RBM47, that interacts with APOBEC1 and A1CF and is expressed in tissues where C to U RNA editing occurs. |
| GO:0005634 nucleus | IDA PMID:24916387 C to U RNA editing mediated by APOBEC1 requires RNA-binding ... | ACCEPT | Summary: A1CF is nuclear, although this paper's cached abstract does not expose its localization assay. Reason: Independent direct localization verifies the term, so the curator call is retained despite incomplete evidence exposure. Supporting Evidence: PMID:12896982 ACF expression is predominantly nuclear, including mutant proteins with deletions of a putative nuclear localization signal. |
| GO:0016554 cytidine to uridine editing | IDA PMID:24916387 C to U RNA editing mediated by APOBEC1 requires RNA-binding ... | ACCEPT | Summary: A1CF can contribute to APOBEC1-dependent C-to-U editing, but RBM47 is often dominant. Reason: The cited paper and later studies support a redundant, tissue-specific A1CF contribution rather than an obligatory role. Supporting Evidence: PMID:24916387 Cytidine (C) to Uridine (U) RNA editing is a post-transcriptional modification that is accomplished by the deaminase APOBEC1 and its partnership with the RNA-binding protein A1CF. PMID:30309881 These data suggest that A1CF and RBM47 each function independently, yet interact in a tissue-specific manner, to regulate the activity and site selection of APOBEC1 dependent C-to-U RNA editing. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-77608 | ACCEPT | Summary: Reactome places A1CF-RNA binding in the nucleus, consistent with nucleoplasmic editosome assembly. Reason: The reaction record and independent localization data support nuclear activity. Supporting Evidence: Reactome:R-HSA-77608 A1CF protein is cytosolic in origin and is translocated to nucleus where it binds to the target RNA. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-77609 | ACCEPT | Summary: Reactome models APOBEC1 joining the A1CF-RNA complex in the nucleoplasm. Reason: The reaction context agrees with A1CF nuclear localization and editosome membership. Supporting Evidence: Reactome:R-HSA-77609 APOBEC-1 binds to ACF:stem-looped mRNA complex forming the editosome (Maris et al.2005). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-83677 | ACCEPT | Summary: Reactome assigns A1CF to a nucleoplasmic deamination reaction, although its cached prose is sparse. Reason: A1CF is noncatalytic; the nucleoplasmic localization is independently supported by HPA and direct nuclear studies. Supporting Evidence: PMID:12896982 ACF expression is predominantly nuclear, including mutant proteins with deletions of a putative nuclear localization signal. |
| GO:0003725 double-stranded RNA binding | IDA NOT PMID:11871661 Identification of domains in apobec-1 complementation factor... | ACCEPT | Summary: Direct assays show that A1CF does not bind double-stranded APOB mRNA with high affinity; they do not exclude every possible dsRNA interaction. Reason: The negated annotation is retained as the curator's record of the tested substrate discrimination, with its APOB-RNA assay scope stated explicitly. Supporting Evidence: PMID:11871661 Here, we show that ACF binds with high affinity to single-stranded but not double-stranded apo-B mRNA. |
| GO:0003727 single-stranded RNA binding | IDA PMID:11871661 Identification of domains in apobec-1 complementation factor... | ACCEPT | Summary: A1CF binds single-stranded APOB mRNA with high affinity. Reason: This is a direct, informative molecular-function assignment. Supporting Evidence: PMID:11871661 Here, we show that ACF binds with high affinity to single-stranded but not double-stranded apo-B mRNA. |
| GO:0005515 protein binding | IPI PMID:10669759 Molecular cloning of apobec-1 complementation factor, a nove... | MODIFY | Summary: A1CF binds the catalytic enzyme APOBEC1 within a functional RNA-editing complex. Reason: Replace generic protein binding with enzyme binding, which preserves the assayed A1CF-APOBEC1 interaction and identifies the partner class. Proposed replacements: enzyme binding Supporting Evidence: PMID:10669759 Coimmunoprecipitation experiments identified an ACF-apobec-1 complex in transfected cells. |
| GO:0005515 protein binding | IPI PMID:12896982 A novel nuclear localization signal in the auxiliary domain ... | MARK AS OVER ANNOTATED | Summary: A1CF directly interacts with nuclear-import carrier TNPO2 through its targeting motif. Reason: The interaction is supported, but generic protein binding is uninformative and no verified specific GO binding term is supplied. Supporting Evidence: PMID:12896982 Co-immunoprecipitation experiments revealed that transportin 2 binds directly to the ANS motif. |
| GO:0005737 cytoplasm | IDA PMID:12881431 The apolipoprotein B mRNA editing complex performs a multifu... | ACCEPT | Summary: A1CF occupies the cytoplasm as well as the nucleus during shuttling. Reason: The cited full text reports cytoplasmic A1CF by microscopy and fractionation. Supporting Evidence: PMID:12881431 In the absence of APOBEC1, we found ACF to localize predominantly to the cytoplasm, with some nuclear localization. |
| GO:0030895 apolipoprotein B mRNA editing enzyme complex | IDA PMID:10781591 Purification and molecular cloning of a novel essential comp... | ACCEPT | Summary: Purified A1CF/ASP complements APOBEC1 and is an APOB mRNA-editing-complex component. Reason: Biochemical reconstitution supports membership, but later mouse genetics shows A1CF is not universally essential in vivo. Supporting Evidence: PMID:10781591 Purified recombinant glutathione S-transferase (GST)-ASP, but not recombinant GST-KSRP, stimulated recombinant GST-APOBEC-1 to edit apoB RNA in vitro. PMID:30309881 These data suggest that A1CF and RBM47 each function independently, yet interact in a tissue-specific manner, to regulate the activity and site selection of APOBEC1 dependent C-to-U RNA editing. |
| GO:0050821 protein stabilization | IDA PMID:12881431 The apolipoprotein B mRNA editing complex performs a multifu... | MODIFY | Summary: The experiment demonstrates stabilization of edited mRNA against NMD, not stabilization of a protein. Reason: The GOA substrate class is wrong; replace it with the specific NMD-regulatory process. Proposed replacements: negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Supporting Evidence: PMID:12881431 The APOBEC1-ACF complex edits and remains associated with the edited RNA to protect it from NMD. |
| GO:1990825 sequence-specific mRNA binding | IDA PMID:10669759 Molecular cloning of apobec-1 complementation factor, a nove... | NEW | Summary: A1CF directly recognizes the defined APOB mooring-sequence region and binds single-stranded APOB mRNA with high affinity. Reason: Existing GOA contains only broader mRNA-, RNA-, and single-stranded RNA-binding terms. The sequence-specific term captures the defining target recognition demonstrated by the mutant-competitor experiment. Supporting Evidence: PMID:10669759 Cross-linking of ACF is not competed by RNAs with mutations in the mooring sequence. PMID:11871661 This complex contains apobec-1, the catalytic subunit, and apobec-1 complementation factor (ACF), the RNA-binding subunit that binds to the mooring sequence. |
| GO:0000381 regulation of alternative mRNA splicing, via spliceosome | IMP PMID:40774250 HNF1A and A1CF coordinate a beta cell transcription-splicing... | NEW | Summary: A1CF loss in human beta-cell models causes widespread alternative-splicing changes, including reduced inclusion of the high-capacity SLC7A2 exon 8 isoform. Reason: Direct human knockout, rescue, and splice-switching experiments establish alternative-splicing regulation as a core physiological A1CF function that is absent from current GOA. Supporting Evidence: PMID:40774250 A1CFKO cells showed profound alternative splicing changes, with 1,907 differentially spliced events in 1,372 genes PMID:31597092 Our results identify a previously unreported function of A1CF as a regulator of alternative splicing of a subset of genes influencing hepatic glucose production through fructose and glycerol metabolism. |
| GO:0035925 mRNA 3'-UTR AU-rich region binding | ISO PMID:20406809 Apobec-1 complementation factor modulates liver regeneration... | NEW | Summary: Mouse A1cf binds an AU-rich region in the IL6 3'-UTR with high affinity. Reason: This experimentally demonstrated activity is proposed for human A1CF by orthology and is retained as a tissue-specific, non-core target-binding function. Supporting Evidence: PMID:20406809 Recombinant ACF bound an AU-rich region in the IL-6 3′-untranslated region with high affinity and IL-6 mRNA half-life was significantly shorter in KC isolated from Acf +/− mice compared with wild-type controls. |
| GO:0070935 3'-UTR-mediated mRNA stabilization | ISO PMID:20406809 Apobec-1 complementation factor modulates liver regeneration... | NEW | Summary: Mouse A1cf stabilizes IL6 mRNA through a 3'-UTR AU-rich region in Kupffer cells after partial hepatectomy. Reason: The mRNA half-life phenotype supports a specific stabilization process by orthology; it is tissue- and transcript-specific rather than a universal A1CF activity. Supporting Evidence: PMID:20406809 Recombinant ACF bound an AU-rich region in the IL-6 3′-untranslated region with high affinity and IL-6 mRNA half-life was significantly shorter in KC isolated from Acf +/− mice compared with wild-type controls. |
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Download this section (compressed HTML)Q: Which endogenous human transcripts are direct A1CF splicing targets in each A1CF-expressing tissue, and which effects are conserved between hepatocytes, beta cells, kidney, and intestine?
Q: Which RNA sequence, structure, binding position, and partner features determine whether A1CF regulates exon choice, stabilizes an mRNA, or presents it to APOBEC1 for editing?
Q: How do A1CF and RBM47 divide and compensate for endogenous APOBEC1-dependent editing targets across human tissues and physiological states?
Q: Do the six reported A1CF isoforms differ in abundance, localization, RNA-target selection, or splicing and editing activity?
Experiment: Introduce an acute endogenous A1CF degron in matched human hepatocyte and beta-cell models, then combine time-resolved eCLIP with short- and long-read RNA sequencing. Rescue from the endogenous locus with wild-type A1CF or an RRM RNA-contact mutant to distinguish direct binding-dependent exon choices from secondary effects.
Hypothesis: A1CF directly controls distinct but partially overlapping alternative-splicing programs in human hepatocytes and pancreatic beta cells.
Experiment: Generate single and double A1CF/RBM47 perturbations in APOBEC1-expressing human intestinal and hepatic organoids, quantify editing transcriptome-wide with orthogonal targeted validation, and rescue each genotype at physiological protein levels. Measure protein abundance and RNA binding to separate compensation from intrinsic substrate preference.
Hypothesis: A1CF and RBM47 have both redundant and substrate-selective roles in endogenous human APOBEC1 editing.
Experiment: Use massively parallel reporters spanning validated APOB, KHK, SLC7A2, and IL6 elements with systematic sequence and structure perturbations, paired with A1CF occupancy measurements and biochemical editing, splicing, and half-life readouts.
Hypothesis: RNA structure and A1CF binding position determine whether a target is spliced, stabilized, or edited.
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