id: O43583
gene_symbol: DENR
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DENR (Density-regulated protein, DRP) is a small cytoplasmic protein containing a C-terminal SUI1 (eIF1-like) domain. Together with its obligate partner MCTS1 it forms the MCTS1-DENR heterodimer, a non-canonical translation factor that is the functional equivalent of eIF2D (Ligatin) split into two polypeptides (MCTS1 corresponds to the N-terminal half, DENR to the C-terminal SUI1 half of Ligatin). The complex acts at the post-termination 40S ribosome to promote translation reinitiation, particularly after translation of short upstream ORFs (uORFs), enabling the small subunit to resume scanning and initiate at a downstream main ORF. Mechanistically the complex (i) promotes dissociation of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated splitting of post-termination complexes, and (ii) recruits aminoacylated initiator tRNA into the ribosomal P-site in an eIF2-independent manner when the start codon is already positioned in the P-site (as on certain HCV-like IRESs and reinitiation events). This activity governs the translation of a defined set of mRNAs (including JAK2), and MCTS1-DENR-dependent reinitiation is required for IFN-gamma immunity.
existing_annotations:
- term:
    id: GO:0001731
    label: formation of translation preinitiation complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic transfer of preinitiation-complex formation, consistent with the experimentally documented role of the MCTS1-DENR complex in assembling tRNA onto 40S/mRNA complexes for (re)initiation.
    action: ACCEPT
    reason: The IBA is corroborated by direct experimental evidence that MCTS1/DENR promotes recruitment of initiator tRNA to 40S/mRNA complexes when the start codon is in the P-site.
    supported_by:
    - reference_id: file:human/DENR/DENR-uniprot.txt
      supporting_text: the recruitment in an EIF2-independent manner of aminoacylated initiator tRNA to P site of 40S ribosomes for a new round of translation
- term:
    id: GO:0002188
    label: translation reinitiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Translation reinitiation is the central, defining biological process of DENR, acting in the MCTS1-DENR complex after short uORFs to allow reinitiation at a downstream ORF. Reinitiation is selective for a subset of uORF-containing transcripts (not global uORF control), and DENR is functionally distinct from its single-chain homolog eIF2D.
    action: ACCEPT
    reason: Strongly supported by both phylogenetic inference and direct experimental evidence (UniProt FUNCTION; ComplexPortal IDA), and is core to DENR function. Recent review/biochemical literature synthesized in the falcon deep research reinforces the uORF-selective reinitiation role of the DENR-MCTS1 complex.
    supported_by:
    - reference_id: file:human/DENR/DENR-uniprot.txt
      supporting_text: Translation regulator forming a complex with MCTS1 to promote translation reinitiation.
    - reference_id: file:human/DENR/DENR-deep-research-falcon.md
      supporting_text: DENR enables post-termination 40S subunits to resume scanning and initiate translation at downstream start codons, most critically at the main ORF of the mRNA
- term:
    id: GO:0002183
    label: cytoplasmic translational initiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Automated (ARBA) assignment of cytoplasmic translational initiation. DENR does participate in cytoplasmic (re)initiation, but its specific role is non-canonical reinitiation/recycling rather than canonical initiation.
    action: KEEP_AS_NON_CORE
    reason: Broadly correct compartment and process, but more general than DENR's specific reinitiation/recycling role; retained as non-core.
    supported_by:
    - reference_id: file:human/DENR/DENR-uniprot.txt
      supporting_text: the recruitment in an EIF2-independent manner of aminoacylated initiator tRNA to P site of 40S ribosomes for a new round of translation
- term:
    id: GO:0003743
    label: translation initiation factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro/SUI1-domain-based assignment of translation initiation factor activity. DENR contributes the SUI1 module of the MCTS1-DENR complex that delivers tRNA to the 40S P-site, so this molecular function is appropriate.
    action: ACCEPT
    reason: The eIF2D-like (re)initiation-factor activity is experimentally established for the MCTS1-DENR complex; DENR is an essential subunit. This is a core molecular function.
    supported_by:
    - reference_id: file:human/DENR/DENR-uniprot.txt
      supporting_text: the recruitment in an EIF2-independent manner of aminoacylated initiator tRNA to P site of 40S ribosomes for a new round of translation
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated cytoplasmic localization, consistent with the experimentally determined cytoplasmic site of action.
    action: ACCEPT
    reason: Agrees with IDA cytoplasm evidence (PMID:16982740); DENR acts on cytoplasmic ribosomes.
    supported_by:
    - reference_id: file:human/DENR/DENR-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0006413
    label: translational initiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: General translational initiation, assigned from the SUI1 domain. DENR's specific role is non-canonical reinitiation and recycling rather than canonical cap-dependent initiation.
    action: KEEP_AS_NON_CORE
    reason: Correct parent process but less informative than the specific reinitiation role; retained as non-core.
    supported_by:
    - reference_id: file:human/DENR/DENR-uniprot.txt
      supporting_text: Translation regulator forming a complex with MCTS1 to promote translation reinitiation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16169070
  qualifier: enables
  review:
    summary: IntAct interaction with MCTS1 (Q9ULC4), DENR's obligate functional partner. The bare protein binding term is uninformative, but the interaction itself is central to DENR function as part of the MCTS1-DENR heterodimer.
    action: KEEP_AS_NON_CORE
    reason: Records a real and functionally pivotal MCTS1 interaction; per curation guidelines bare protein binding is not elevated to core, but the heterodimerization is captured in core_functions.
    supported_by:
    - reference_id: file:human/DENR/DENR-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16169070 UniProtKB:Q9ULC4
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16874301
  qualifier: enables
  review:
    summary: IntAct interactions with UBC (P0CG48) and MARCHF5 (Q9NX47) from a high-throughput screen, unrelated to DENR's reinitiation function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding from high-throughput screens with partners not connected to the MCTS1-DENR reinitiation/recycling function; uninformative and non-core.
    supported_by:
    - reference_id: file:human/DENR/DENR-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16874301 UniProtKB:Q9NX47
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16936636
  qualifier: enables
  review:
    summary: IntAct interactions with UBC (P0CG48) and MARCHF5 (Q9NX47); high-throughput, not connected to DENR's translation function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding from high-throughput screens with partners unrelated to reinitiation; uninformative and non-core.
    supported_by:
    - reference_id: file:human/DENR/DENR-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16936636 UniProtKB:Q9NX47
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20195357
  qualifier: enables
  review:
    summary: IntAct interaction with NELFB (Q8WX92) from a high-throughput screen; not related to DENR's reinitiation/recycling function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding from a high-throughput screen with a partner unrelated to DENR's core function; uninformative.
    supported_by:
    - reference_id: file:human/DENR/DENR-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20195357 UniProtKB:Q8WX92
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21516116
  qualifier: enables
  review:
    summary: IntAct interaction with MCTS1 (Q9ULC4), the obligate DENR partner.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally central MCTS1 interaction; bare protein binding is not elevated to core but the heterodimer is captured in core_functions.
    supported_by:
    - reference_id: file:human/DENR/DENR-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21516116 UniProtKB:Q9ULC4
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: IntAct interaction with MCTS1 (Q9ULC4), the obligate DENR partner.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally central MCTS1 interaction; bare protein binding is not elevated to core but the heterodimer is captured in core_functions.
    supported_by:
    - reference_id: file:human/DENR/DENR-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:Q9ULC4
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex interactions including MCTS1 (Q9ULC4) and MAPT/tau (P10636). The MCTS1 interaction is functionally central; the tau interaction is a high-throughput observation.
    action: KEEP_AS_NON_CORE
    reason: Captures the functionally central MCTS1 interaction (alongside a peripheral tau hit); bare protein binding is not elevated to core.
    supported_by:
    - reference_id: file:human/DENR/DENR-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q9ULC4
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34757590
  qualifier: enables
  review:
    summary: IntAct interaction with MAPT/tau (P10636) from a high-throughput study; not connected to DENR's reinitiation function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding from a high-throughput screen with tau, unrelated to DENR's core function; uninformative.
    supported_by:
    - reference_id: file:human/DENR/DENR-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:34757590 UniProtKB:P10636
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Cell-maps interactome interaction with MCTS1 (Q9ULC4), the obligate DENR partner.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally central MCTS1 interaction; bare protein binding is not elevated to core but is captured in core_functions.
    supported_by:
    - reference_id: file:human/DENR/DENR-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q9ULC4
- term:
    id: GO:0002188
    label: translation reinitiation
  evidence_type: IDA
  original_reference_id: PMID:37875108
  qualifier: involved_in
  review:
    summary: Direct evidence (ComplexPortal/IDA) that the MCTS1-DENR complex mediates translation reinitiation, demonstrated for JAK2 and other targets.
    action: ACCEPT
    reason: Direct experimental support for the core reinitiation function of DENR within the MCTS1-DENR complex.
    supported_by:
    - reference_id: file:human/DENR/DENR-uniprot.txt
      supporting_text: Translation regulator forming a complex with MCTS1 to promote translation reinitiation.
- term:
    id: GO:0070992
    label: translation initiation complex
  evidence_type: IPI
  original_reference_id: PMID:29889857
  qualifier: part_of
  review:
    summary: DENR is part of the MCTS1-DENR (re)initiation complex; heterodimerization with MCTS1 and tRNA recruitment are required for reinitiation.
    action: ACCEPT
    reason: Supported by structural/biochemical demonstration that DENR-MCTS1 heterodimerize to form the functional reinitiation complex.
    supported_by:
    - reference_id: PMID:29889857
      supporting_text: DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16982740
  qualifier: enables
  review:
    summary: UniProt-curated interaction with MCTS1 (Q9ULC4); this is the foundational report that DENR/DRP is recruited by MCTS1 via the PUA/SUI1 interface.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally central MCTS1 interaction; bare protein binding is not elevated to core but the heterodimer is captured in core_functions.
    supported_by:
    - reference_id: PMID:16982740
      supporting_text: recruits the density-regulated protein (DENR/DRP), containing the SUI1 translation initiation domain
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:16982740
  qualifier: is_active_in
  review:
    summary: Direct evidence that DENR is active in the cytoplasm, where it associates with the cap complex/translation machinery via MCTS1.
    action: ACCEPT
    reason: IDA-supported cytoplasmic site of action, consistent with DENR's role on cytoplasmic ribosomes.
    supported_by:
    - reference_id: file:human/DENR/DENR-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0075522
    label: IRES-dependent viral translational initiation
  evidence_type: IDA
  original_reference_id: PMID:20713520
  qualifier: involved_in
  review:
    summary: MCT-1/DENR promotes eIF2-independent recruitment of initiator tRNA on HCV-like IRESs and SV 26S mRNA, where the start codon is placed directly in the P-site.
    action: KEEP_AS_NON_CORE
    reason: A genuine but specialized application of DENR's P-site tRNA delivery activity (viral IRES context); retained as non-core relative to cellular reinitiation.
    supported_by:
    - reference_id: PMID:20713520
      supporting_text: promote efficient eIF2-independent recruitment of Met-tRNA(Met)(i) to 40S/mRNA complexes, if attachment of 40S subunits to the mRNA places the initiation codon directly in the P site, as on HCV-like IRESs
- term:
    id: GO:0001731
    label: formation of translation preinitiation complex
  evidence_type: IDA
  original_reference_id: PMID:20713520
  qualifier: involved_in
  review:
    summary: Direct evidence that MCT-1/DENR assembles initiator tRNA onto 40S/mRNA complexes, forming a preinitiation-type complex for reinitiation/recycling.
    action: ACCEPT
    reason: Direct experimental support for DENR's role in assembling the tRNA-loaded 40S complex.
    supported_by:
    - reference_id: PMID:20713520
      supporting_text: promote efficient eIF2-independent recruitment of Met-tRNA(Met)(i) to 40S/mRNA complexes
- term:
    id: GO:0032790
    label: ribosome disassembly
  evidence_type: IDA
  original_reference_id: PMID:20713520
  qualifier: involved_in
  review:
    summary: MCT-1/DENR promotes release of deacylated tRNA and mRNA from recycled 40S subunits after ABCE1-mediated splitting of post-termination ribosomes, i.e. the recycling/recovery step. Recent reviews reinforce that this tRNA-release/40S-recycling activity (a property of the DENR-MCTS1 complex) is a defining function and that penultimate-codon identity in the uORF modulates the efficiency of DENR-MCTS1-dependent recycling.
    action: ACCEPT
    reason: Direct experimental support for DENR's role in 40S recycling (clearing deacylated tRNA/mRNA), a core part of its function, corroborated by recent review literature synthesized in the falcon deep research. Recycling is a property of the DENR-MCTS1 heterodimer, of which DENR is the essential SUI1-bearing subunit.
    supported_by:
    - reference_id: PMID:20713520
      supporting_text: Ligatin and MCT-1/DENR can promote release of deacylated tRNA and mRNA from recycled 40S subunits after ABCE1-mediated dissociation of post-termination ribosomes
    - reference_id: file:human/DENR/DENR-deep-research-falcon.md
      supporting_text: This tRNA release is essential for 40S ribosome dissociation from mRNA and recycling back into the translational pool
references:
- id: file:human/DENR/DENR-deep-research-falcon.md
  title: Falcon deep research report for DENR
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: 'LLM-synthesized deep-research report (Edison/Falcon). DENR-specific claims
      that are well-anchored to the primary literature and consistent with the curated picture:
      DENR is a non-canonical translation factor acting only as part of the DENR-MCTS1 (or
      DENR-MCTS2) heterodimer; core activities are post-termination 40S recycling (release of
      deacylated tRNA from the P-site) and reinitiation after short uORFs; cytoplasmic, ribosome-associated
      localization with stress-granule relocalization under oxidative (arsenite) stress; cell-cycle
      regulation via Ser73 phosphorylation by Cyclin B/CDK1 and Cyclin A/CDK2. CAVEAT: the report
      frequently attributes the heterodimer''s biochemical activities to "DENR" alone; recycling/reinitiation/tRNA-handling
      are properties of the DENR-MCTS1 complex, of which DENR contributes the SUI1/eIF1-like half.
      Pathway/disease claims (ATF4/ISR, JAK2/IFN-gamma immunity, mitotic translation, RAN-translation
      suppression, neurodevelopment) are largely heterodimer- or MCTS1-centric inferences and not
      DENR-only molecular functions. Underlying PMIDs not individually verified here (report cites by
      internal keys, not PMIDs), hence UNVERIFIED.'
  findings:
  - statement: The DENR-MCTS1 complex acts on post-termination 40S ribosomal subunits to facilitate
      removal of deacylated tRNA from the P-site, which is essential for 40S dissociation from mRNA
      and recycling back into the translational pool.
    reference_section_type: OTHER
  - statement: DENR-MCTS1 promotes translation reinitiation, particularly after short uORFs in 5'UTRs,
      and this reinitiation is selective for only a subset of uORF-containing transcripts; DENR is functionally
      distinct from its single-chain homolog eIF2D.
    reference_section_type: OTHER
  - statement: Under oxidative (arsenite) stress, DENR relocalizes together with MCTS1, eIF2D, ABCE1,
      eRF1 and eRF3 to cytoplasmic stress granules, suggesting spatial regulation of post-termination/reinitiation
      factors during stress.
    reference_section_type: OTHER
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:16169070
  title: 'A human protein-protein interaction network: a resource for annotating the proteome.'
  findings: []
- id: PMID:16874301
  title: A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics.
  findings: []
- id: PMID:16936636
  title: MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology.
  findings: []
- id: PMID:16982740
  title: MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles.
  findings:
  - statement: MCT-1 (MCTS1) interacts with the cap complex through its PUA domain and recruits DENR/DRP, which contains the SUI1 translation initiation domain.
    reference_section_type: ABSTRACT
- id: PMID:20195357
  title: A comprehensive resource of interacting protein regions for refining human transcription factor networks.
  findings: []
- id: PMID:20713520
  title: Activities of Ligatin and MCT-1/DENR in eukaryotic translation initiation and ribosomal recycling.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches; abstract establishes the eIF2-independent initiator-tRNA recruitment and 40S recycling activities of MCT-1/DENR, directly supporting DENR's core reinitiation/recycling function.
  findings:
  - statement: MCT-1 and DENR (homologous to N- and C-terminal regions of Ligatin) together promote eIF2-independent recruitment of initiator tRNA to 40S/mRNA complexes when the initiation codon is placed directly in the P-site.
    reference_section_type: ABSTRACT
  - statement: MCT-1/DENR can promote release of deacylated tRNA and mRNA from recycled 40S subunits after ABCE1-mediated dissociation of post-termination ribosomes.
    reference_section_type: ABSTRACT
- id: PMID:21516116
  title: Next-generation sequencing to generate interactome datasets.
  findings: []
- id: PMID:29889857
  title: DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches; establishes that DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation, directly supporting DENR's core function.
  findings:
  - statement: DENR and MCTS1 heterodimerize and this, together with tRNA recruitment, is required for translation reinitiation.
    reference_section_type: TITLE
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:34757590
  title: Targeting Tau Mitigates Mitochondrial Fragmentation and Oxidative Stress in Amyotrophic Lateral Sclerosis.
  findings: []
- id: PMID:37875108
  title: Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria.
  findings:
  - statement: MCTS1-DENR-dependent translation reinitiation is required for translation of JAK2 and for IFN-gamma immunity to mycobacteria.
    reference_section_type: ABSTRACT
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
core_functions:
- description: As an essential subunit of the MCTS1-DENR heterodimer (an eIF2D-like non-canonical factor), provides the SUI1 module that delivers aminoacylated tRNA into the 40S ribosomal P-site in an eIF2-independent manner to drive translation reinitiation after short uORFs.
  molecular_function:
    id: GO:0003743
    label: translation initiation factor activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/DENR/DENR-uniprot.txt
    supporting_text: the recruitment in an EIF2-independent manner of aminoacylated initiator tRNA to P site of 40S ribosomes for a new round of translation
  - reference_id: PMID:29889857
    supporting_text: DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation
- description: Within the MCTS1-DENR complex, promotes recycling/recovery of post-termination 40S subunits by promoting dissociation of deacylated tRNA and mRNA after ABCE1-mediated ribosome splitting.
  molecular_function:
    id: GO:0003743
    label: translation initiation factor activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:20713520
    supporting_text: Ligatin and MCT-1/DENR can promote release of deacylated tRNA and mRNA from recycled 40S subunits after ABCE1-mediated dissociation of post-termination ribosomes
  - reference_id: file:human/DENR/DENR-deep-research-falcon.md
    supporting_text: to facilitate the removal of deacylated tRNA from the ribosomal P-site
proposed_new_terms: []
suggested_questions:
- question: What determines the subset of >150 mRNAs whose reinitiation depends on MCTS1-DENR, and do uORF features (length, Kozak context, terminator distance) predict dependence?
- question: Does phosphorylation of DENR (Ser-73 and other mitotic sites) regulate MCTS1-DENR complex assembly or reinitiation activity?
- question: To what extent can the MCTS1 paralog MCTS2 substitute for MCTS1 as a DENR partner in vivo, and does DENR-MCTS2 have distinct transcript selectivity from DENR-MCTS1?
suggested_experiments:
- description: Ribosome profiling in DENR-knockout versus wild-type cells to map reinitiation-dependent mORFs genome-wide and define uORF determinants of MCTS1-DENR dependence.
- description: Reconstituted 40S recycling assays with purified DENR/MCTS1, ABCE1 and post-termination complexes to quantify the kinetics of deacylated tRNA/mRNA release contributed by DENR.