Affinage

LARP1

La-related protein 1 · UniProt Q6PKG0

Length
1096 aa
Mass
123.5 kDa
Annotated
2026-06-10
83 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LARP1 is an mTORC1-regulated, phosphorylation-sensitive RNA-binding protein that serves as the principal post-transcriptional controller of 5'TOP mRNAs encoding ribosomal proteins and translation factors (PMID:25940091, PMID:28650797, PMID:32094190). It operates as a bipartite molecular switch: its C-terminal DM15 (HEAT-repeat) domain directly engages both the m7G cap and the adjacent 5'TOP motif, sterically blocking eIF4E/eIF4F assembly and repressing translation when mTORC1 is inactive, with binding specificity driven by an invariant pocket that reads the +1 cytidine characteristic of TOP transcripts (PMID:28379136, PMID:31676287, PMID:29244122). mTORC1 (and Akt/S6K1) directly phosphorylate LARP1 at multiple clustered serine/threonine residues, and phosphorylation near the DM15 region dissociates LARP1 from the 5'-end to relieve repression (PMID:28650797, PMID:33398329). In parallel, its N-terminal La-module — through a La-motif that binds poly(A) 3'-ends and a PAM2 motif that docks onto the MLLE domain of cytoplasmic PABP — protects poly(A) tails and stabilizes TOP mRNAs, decelerating CCR4-NOT-mediated deadenylation by forming a LARP1–PABP–poly(A) ternary complex (PMID:33398329, PMID:33292040, PMID:35979957, PMID:36849640, PMID:41762867). Beyond translational repression per se, live-cell and transcriptome analyses establish that under mTOR inhibition LARP1's dominant function is selective protection of 5'TOP mRNAs from degradation, preserving the TOP regulon for rapid recovery, while a newly defined RRM domain couples LARP1 to non-translating 40S/80S ribosomal subunits to license TOP engagement (PMID:38363833, PMID:39533057, PMID:42039457). LARP1 broadly stabilizes and tunes specific transcripts in cancer and tissue contexts — including BCL2/BIK, mTOR, MYC, and SERCA2a (ATP2A2) mRNAs — linking it to apoptosis resistance, proliferation, and cardiac remodeling (PMID:26717985, PMID:25531318, PMID:35195778, PMID:41126333), and brain-specific loss depletes synaptic TOP mRNAs and impairs spatial memory (PMID:41278816).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2008 Medium

    Established LARP1 orthologs as RNA-binding, PABP-associated post-transcriptional regulators with conserved developmental roles, framing the protein family before its mammalian translational function was known.

    Evidence C. elegans larp-1 genetics, in vitro RNA binding via La motif and LARP1 domain, P-body localization; Drosophila Larp-PABP Co-IP and mitotic/meiotic phenotypes

    PMID:18515547 PMID:19631203 PMID:20663921

    Open questions at the time
    • Direct molecular targets in mammals not yet defined
    • TOP mRNA connection not yet made
    • ortholog phenotypes not mechanistically linked to translation
  2. 2010 High

    Placed mammalian LARP1 physically within the translation apparatus and showed it is required for global protein synthesis, defining it as a translation-associated factor rather than a generic RNA-binding protein.

    Evidence Co-IP of LARP1-PABP-eIF4E complex, sucrose-gradient ribosome association (60S/80S), siRNA knockdown with mitotic arrest and migration defects

    PMID:20430826

    Open questions at the time
    • Specific mRNA targets not identified
    • no mechanism for how LARP1 acts on ribosomes
    • directness of eIF4E association unresolved
  3. 2014 High

    Identified the transcriptome-scale LARP1 interactome and linked LARP1 to 5'TOP mRNAs and mTORC1, establishing it as a specific regulator of the TOP regulon and cancer-relevant transcripts.

    Evidence Cap-binding proteomic screen, RIP-seq (~3000 mRNAs), polysome profiling, mTORC1 Co-IP, functional siRNA with growth/invasion readouts

    PMID:24532714 PMID:25531318

    Open questions at the time
    • Whether LARP1 activates or represses TOP translation was initially ambiguous
    • no structural basis for RNA recognition
    • phosphoregulation not yet shown
  4. 2015 High

    Resolved LARP1 as an mTORC1-dependent repressor that competes with eIF4G for TOP mRNAs, and extended its target stabilization to apoptosis-regulating mRNAs in cancer.

    Evidence LARP1-RAPTOR Co-IP, mTORC1-dependent RIP, eIF4G competition assay, siRNA rescue of rapamycin/Torin1 effects; RIP and stability assays for BCL2/BIK in ovarian cancer with xenografts

    PMID:25940091 PMID:26717985

    Open questions at the time
    • Phosphorylation sites mediating mTORC1 control not mapped
    • no atomic-resolution view of cap/TOP recognition
    • reconciliation of repressor vs stabilizer roles incomplete
  5. 2017 High

    Defined LARP1 as a direct mTORC1/Akt-S6K1 substrate whose phosphorylation acts as the switch between repression and translation-competence, providing the kinase logic of the system.

    Evidence In vitro kinase assays, iCLIP/PAR-CLIP of LARP1-bound 5' and 3'UTRs, phospho-mutant analysis, polysome profiling

    PMID:28650797

    Open questions at the time
    • Functional role of each phospho-cluster not separated
    • scaffolding model for mTORC1 on 3'UTRs needs structural support
  6. 2018 High

    Established the structural and biochemical basis for cap-dependent TOP repression: the DM15 domain binds m7G cap and the adjacent TOP motif to occlude eIF4E, and the C-terminal half is sufficient to repress in vitro.

    Evidence X-ray structures of DM15 with m7GTP, m7GpppC and TOP motif; cap-binding competition; purified-LARP1 in vitro repression and domain truncation

    PMID:28379136 PMID:29244122 PMID:31676287

    Open questions at the time
    • Mechanism of phospho-release at the structural level not captured
    • role of N-terminal La-module in repression not yet integrated
  7. 2020 High

    Bisected the LARP1 mechanism into a constitutive PABP-bound La-module and a regulated DM15 'pendular hook', and demonstrated genome-wide that LARP1 is the primary TOP-mRNA translation regulator.

    Evidence mTORC1 phosphoproteomics (26 sites/7 clusters), phospho-mutant RNA-binding assays; La-module EMSA/FP binding to TOP and poly(A); PAM2 mutagenesis with in vivo poly(A) protection; Ribo-seq in LARP1 KO across 16 tissues (TOPscore)

    PMID:31601159 PMID:32094190 PMID:33292040 PMID:33398329

    Open questions at the time
    • In vitro vs in vivo discrepancy in La-module RNA binding (PAM2 mutant)
    • how phospho-clusters quantitatively tune affinity unresolved
  8. 2021 Medium

    Showed PABPC1 dependence of LARP1 target selection and a role for LARP1-40S complexes in protecting the TOP regulon from ribophagy, broadening LARP1 from translational control toward mRNA preservation under stress.

    Evidence RBP capture-seq with PABPC1 depletion, Co-IP, polysome profiling; ribosome fractionation, RNA-seq of LARP1-40S complexes, ribophagy assays under mTOR inhibition

    PMID:33332560 PMID:34818049

    Open questions at the time
    • Single-lab findings
    • direct ribosome-binding interface not defined here
    • mechanism coupling 40S to ribophagy protection unresolved
  9. 2022 Medium

    Provided crystallographic proof that the LaM domain alone binds poly(A) 3'-ends with submicromolar specificity and uncovered LARP1's control of TOP poly(A) dynamics, plus a GCN2/ATF4 input that converges on LARP1.

    Evidence LaM-poly(A) crystal structures with mutagenesis and cellular poly(A) protection; poly(A) tail-seq with non-canonical poly(A) polymerase Co-IP; GCN2 KO MEFs, ATF4 ChIP-seq, GCN1-LARP1 Co-IP on stalled ribosomes; MYC 3'UTR feedback loop with IGF2BP3/YBX1 interactors

    PMID:35195778 PMID:35863436 PMID:35979957 PMID:36288708

    Open questions at the time
    • Identity of non-canonical poly(A) polymerases partnering LARP1 not fully defined
    • GCN1-LARP1 recruitment mechanism single-lab
    • MYC feedback loop generality unknown
  10. 2023 High

    Reconstituted LARP1 as a sequence-window-specific decelerator of deadenylation, showing it forms a ternary complex with PABP and poly(A) to antagonize CCR4-NOT and broadly stabilize mRNAs.

    Evidence Poly(A) pulse-chase in cells, LARP1 KD with poly(A) and abundance readouts, in vitro deadenylation with purified CCR4-NOT and LARP1; O-GlcNAc/TRIM25 PTM control of LARP1 stability with DKK4 mRNA stabilization

    PMID:36849640 PMID:37070251

    Open questions at the time
    • Why LARP1 acts preferentially in the 30-60 nt window mechanistically unclear
    • PTM regulation single-lab and context-specific
  11. 2024 High

    Refined the division of labor in mTOR-inhibited cells (4EBP1/2 represses translation, LARP1 protects TOP mRNAs from degradation), identified the LARP1-40S/80S ribosome interface by cryo-EM, and added eIF4A1 and PAM2-MLLE structural detail.

    Evidence Single-molecule SunTag imaging with half-life analysis and KOs; cryo-EM of LARP1-40S/80S with mRNA-channel occlusion and ribosome-binding mutants; eIF4A1 RNA pulldown-seq and Ribo-seq; NMR/ITC of non-canonical PAM2 helix (F496); LaM crystal structures with guanylated poly(A)

    PMID:38363833 PMID:38773334 PMID:39016322 PMID:39533057 PMID:41762867

    Open questions at the time
    • Cryo-EM study found ribosome binding NOT required for repression/stabilization, conflicting with later RRM model
    • physiological role of guanine-tolerant poly(A) recognition unclear
  12. 2025 Medium

    Extended LARP1 function to physiology and disease: brain-specific loss depletes synaptic TOP mRNAs and impairs memory; LARP1 stabilizes SERCA2a mRNA to limit cardiac remodeling; and it acts as an antiviral factor cleaved by EV-D68 protease.

    Evidence Brain-specific Larp1 cKO mice with RNA-seq, synaptic fractionation and behavior (preprint); LARP1 KO/AAV9 overexpression with ATP2A2 RIP/pull-down rescue in heart; EV-D68 5'UTR-LAM domain mapping with overexpression/KD and 3Cpro cleavage assays

    PMID:40294010 PMID:41126333 PMID:41278816

    Open questions at the time
    • Brain study is a preprint
    • tissue-specific target selectivity mechanisms not defined
    • antiviral specificity across enteroviruses untested
  13. 2026 Medium

    Identified the LARP1 ribosome-binding region as an RRM domain that intramolecularly engages DM15, proposing that ribosome sensing via RRM remodeling licenses TOP binding, repression and stabilization.

    Evidence Cryo-EM identification of RRM, in vitro ribosome-binding reconstitution, RRM mutagenesis with TOP repression/stability and cell-fitness readouts (preprint)

    PMID:42039457

    Open questions at the time
    • Preprint, not peer-reviewed
    • directly conflicts with prior finding that ribosome binding is not required for repression/stabilization
    • in vivo relevance of RRM-DM15 interplay untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the structurally defined inputs (phospho-clusters, RRM-ribosome sensing, eIF4A1, PABP) are quantitatively integrated to set the repression-vs-protection balance for individual TOP and non-TOP transcripts across tissues.
  • Conflicting evidence on whether ribosome binding is required for TOP regulation
  • no unified model linking phosphostate to differential target fate
  • lysosomal TOP-mRNA delivery role rests on a single low-confidence preprint

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0045182 translation regulator activity 4 GO:0140110 transcription regulator activity 4 GO:0098772 molecular function regulator activity 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005840 ribosome 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953854 Metabolism of RNA 3
Partners
EIF4A1EIF4EGCN1IGF2BP3PABPC1RAPTORYBX1
Complex memberships
LARP1-40S/80S ribosome complexLARP1-PABP-eIF4E cap-binding complexLARP1-PABP-poly(A) ternary complex (anti-CCR4-NOT)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 LARP1 functions as a repressor of TOP mRNA translation downstream of mTORC1: it associates with mTORC1 via RAPTOR, binds the 5'TOP motif of TOP mRNAs in an mTORC1-dependent manner, and competes with eIF4G for TOP mRNA binding. siRNA knockdown of LARP1 attenuates the inhibitory effect of rapamycin, Torin1, and amino acid deprivation on TOP mRNA translation. Co-immunoprecipitation (LARP1-RAPTOR), RNA immunoprecipitation, competition binding assays, siRNA knockdown with translation readouts, pharmacological mTORC1 inhibition The Journal of biological chemistry High 25940091
2014 LARP1 associates with actively translating ribosomes via PABP, associates with mTORC1, and is required for global protein synthesis as well as cell growth and proliferation. It stimulates translation of mRNAs containing a 5'TOP motif. Quantitative proteomic cap-binding screen (m7G cap pulldown), co-immunoprecipitation, polysome profiling, siRNA knockdown with cell growth/proliferation readouts Genes & development High 24532714
2017 LARP1 is a direct substrate of mTORC1 and Akt/S6K1. Non-phosphorylated LARP1 interacts with both 5' and 3'UTRs of ribosomal protein mRNAs and inhibits their translation. Phosphorylation of LARP1 by mTORC1 and Akt/S6K1 dissociates it from 5'UTRs and relieves translational inhibition. Phosphorylated LARP1 then scaffolds mTORC1 on 3'UTRs of translationally competent RP mRNAs to facilitate mTORC1-dependent translation initiation. In vitro kinase assays (direct substrate validation), deep sequencing of LARP1-bound mRNAs (iCLIP/PAR-CLIP), phospho-mutant analysis, polysome profiling eLife High 28650797
2017 Crystal structures of the human LARP1 DM15 region in complex with a 5'TOP motif, cap analog (m7GTP), and capped cytidine (m7GpppC) show that LARP1 directly binds the m7G cap and adjacent 5'TOP motif. This binding effectively impedes access of eIF4E to the cap, preventing eIF4F assembly on TOP mRNAs. X-ray crystallography (2.6, 1.8, and 1.7 Å resolution structures), cap-binding competition assays, immunoprecipitation eLife High 28379136
2018 The C-terminal half of LARP1 (containing the DM15 cap-binding domain and an adjacent regulatory region) is necessary and sufficient to control TOP mRNA translation. Purified LARP1 represses TOP mRNA translation in vitro through combined recognition of both the TOP sequence and cap structure. Domain deletion/truncation analysis in cells, in vitro translation repression assay with purified LARP1, binding affinity measurements Nucleic acids research High 29244122
2021 mTORC1 phosphorylates LARP1 in vitro and in vivo at 26 rapamycin-sensitive phospho-serine/threonine residues distributed in 7 clusters. Phosphorylation of a cluster of residues proximal to the DM15 cap-binding region is particularly rapamycin-sensitive and regulates both RNA-binding and translation inhibitory activities. The La module (LaMod) remains constitutively bound to PABP regardless of mTORC1 activation status, while the DM15 'pendular hook' engages the TOP mRNA 5'-end to repress translation only when mTORC1 is inhibited. In vitro mTORC1 kinase assay, quantitative phosphoproteomics (mass spectrometry), phospho-mutant functional analysis, RNA binding assays, rapamycin/torin1 treatment Nucleic acids research High 33398329
2019 Molecular dynamics simulations, biophysical assays, and X-ray crystallography reveal the mechanism of DM15 binding to TOP transcripts: residues C-terminal to the m7G-binding site play important roles in cap recognition, and an unusually static pocket that recognizes the +1 cytosine characteristic of TOP transcripts drives binding specificity. X-ray crystallography, molecular dynamics simulations, biophysical binding assays (ITC/SPR) Structure (London, England : 1993) High 31676287
2010 Mammalian LARP1 is found in a complex with poly(A)-binding protein (PABP) and eukaryotic initiation factor 4E (eIF4E), and is associated with 60S and 80S ribosomal subunits. siRNA-mediated reduction of LARP1 inhibits global protein synthesis, causes mitotic arrest, and delays cell migration. LARP1 protein localizes to the leading edge of migrating cells and interacts with cytoskeletal components. Co-immunoprecipitation (LARP1-PABP-eIF4E complex), sucrose gradient sedimentation (ribosome association), siRNA knockdown, immunofluorescence localization, cell migration assays Nucleic acids research High 20430826
2013 LARP1 specifically recognizes the 3' termini of normal poly(A) tails (identified by proteomics of poly(A)-tail-associated proteins) and stabilizes multiple mRNAs carrying 5'TOP sequences. Proteomics-based identification of poly(A)-terminus-binding proteins, mRNA stability assays following LARP1 manipulation FEBS letters Medium 23711370
2015 LARP1 interacts with the 3'UTRs of BCL2 and BIK mRNAs, stabilizing BCL2 mRNA but destabilizing BIK mRNA, with the net effect of resisting apoptosis in ovarian cancer cells. LARP1 knockdown reduces cancer cell survival and chemotherapy resistance. RNA immunoprecipitation (RIP), mRNA stability assays, siRNA knockdown, xenograft tumor models, transcriptomic analysis cross-referenced against LARP1 interactome Nucleic acids research Medium 26717985
2014 LARP1 is complexed to ~3000 mRNAs enriched for cancer pathways. mTOR mRNA is a prominent member of the LARP1 interactome and is stabilized by LARP1. LARP1 promotes cell migration, invasion, and anchorage-independent growth. RNA immunoprecipitation followed by sequencing (RIP-seq), mRNA stability assays, siRNA knockdown with migration/invasion/anchorage-independent growth assays Oncogene Medium 25531318
2019 The LARP1 La-Module (N-terminal region) binds TOP motifs in a cap-independent manner and also recognizes poly(A) RNA. The La-Module can simultaneously engage TOP motifs and poly(A) RNA, suggesting LARP1 can bridge both ends of TOP mRNAs. Electrophoretic mobility shift assays (EMSA), fluorescence polarization binding assays, in vitro RNA binding with purified La-Module RNA biology Medium 31601159
2020 LARP1 is established as the primary translation regulator of mRNAs with classical TOP motifs genome-wide. The DM15 cap-binding domain and TOP sequence features together determine regulatory potency. Analysis across 16 mammalian tissues reveals constitutive and tissue-specific sets of TOP mRNAs regulated by LARP1. Genome-wide ribosome profiling (Ribo-seq), LARP1 knockout/knockdown coupled with transcriptome-wide translation analysis, quantitative TOPscore metric development Proceedings of the National Academy of Sciences of the United States of America High 32094190
2020 The isolated La-module of LARP1 mediates poly(A) length protection and mRNA stabilization in HEK293 cells, dependent on a PAM2 motif that binds PABP. A point mutation in the PAM2 motif impairs mRNA stabilization and PABP binding in vivo, but does not impair oligo(A) RNA binding by the purified recombinant La-module in vitro. In vivo mRNA stabilization assay, poly(A) length protection assay, co-immunoprecipitation, point mutagenesis of PAM2 motif, in vitro RNA binding with purified protein RNA biology High 33292040
2022 Crystal structures of the LARP1 La motif (LaM) domain in complex with poly(A) RNA show the LaM alone (without an RRM) is sufficient for binding poly(A) RNA with submicromolar affinity and specificity, with highest specificity for the RNA 3'-end. Residues Q333, Y336, and F348 are critical for binding. LARP1 La-module binding has functional relevance for poly(A) 3' protection in cells. X-ray crystallography (multiple high-resolution structures with different RNA ligands), ITC binding measurements, mutagenesis of critical residues, quantitative mRNA stabilization assay, poly(A) tail-sequencing in cells Nucleic acids research High 35979957
2022 TOP mRNA translation positively correlates with poly(A) tail length under mTOR-active conditions. LARP1 is indispensable for mTOR-regulated poly(A) tail-length dynamics: under amino-acid-starved/mTOR-inactive conditions, LARP1 interacts with non-canonical poly(A) polymerases to induce post-transcriptional polyadenylation of TOP mRNA targets, leading to accumulation of long-tailed TOP mRNAs and accelerated ribosomal loading upon nutrient recovery. Poly(A) tail-length sequencing, polysome profiling, co-immunoprecipitation (LARP1 with poly(A) polymerases), LARP1 knockout/knockdown with poly(A) length readouts Cell reports Medium 36288708
2021 LARP1 complexed with the 40S ribosomal subunit protects TOP mRNA regulon from ribophagy under mTOR inhibition, preserving the translatome capacity for ribosome biogenesis resumption when growth conditions return permissive. Ribosome fractionation, RNA sequencing of LARP1-40S complex-associated mRNAs, ribophagy assays, mTOR inhibition experiments Science advances Medium 34818049
2021 PABPC1 is required for the association of LARP1 with its specific mRNA targets. Non-TOP-containing mRNAs bound by LARP1 are in a translationally-repressed state even under control conditions. mRNAs bound by both LARP1 and PABPC1 are translationally repressed. RNA-binding protein capture upon mTOR inhibition (RBP capture-seq), co-immunoprecipitation, PABPC1 depletion with LARP1 mRNA-binding readout, polysome profiling Nucleic acids research Medium 33332560
2023 LARP1 acts as a general decelerator of deadenylation specifically in the 30–60 nucleotide poly(A) length window by preferentially associating with short poly(A) tails. LARP1 depletion causes accelerated deadenylation in the 30–60 nt range and global reduction of mRNA abundance. LARP1 interferes with CCR4-NOT-mediated deadenylation in vitro by forming a ternary complex with PABP and poly(A). Poly(A) tail-length pulse-chase measurement, LARP1 knockdown with poly(A) length and mRNA abundance readouts, in vitro deadenylation assay with purified CCR4-NOT and LARP1 Nature structural & molecular biology High 36849640
2024 Cryo-EM structures reveal that a previously uncharacterized domain of LARP1 directly binds to and occludes the mRNA channel of the 40S ribosomal subunit. Increased availability of free ribosomal subunits promotes 60S joining at the same interface to form LARP1-80S complexes. Contrary to expectations, ribosome binding is NOT required for LARP1-mediated TOP repression or stabilization. Cryo-EM structural determination of LARP1-40S and LARP1-80S complexes, domain mutagenesis to disrupt ribosome binding, functional TOP mRNA repression and stability assays The EMBO journal High 39533057
2024 4EBP1/2 has a dominant role in translational repression of both 5'TOP and canonical mRNAs during pharmacological mTOR inhibition, whereas LARP1 selectively protects 5'TOP mRNAs from degradation rather than primarily repressing their translation. Single-molecule translation site imaging shows this distinction in living cells. Single-molecule translation site imaging (SunTag reporter), transcriptome-wide mRNA half-life analysis, LARP1 and 4EBP1/2 knockouts/knockdowns Science advances High 38363833
2024 eIF4A1 enhances LARP1-mediated translational repression of TOP mRNAs during mTORC1 inhibition. eIF4A1 preferentially binds TOP mRNAs in a LARP1-dependent manner and increases the interaction between TOP mRNAs and LARP1, thereby strengthening translational repression upon mTORC1 inhibition. RNA pulldown followed by sequencing, ribosome profiling, co-immunoprecipitation, EIF4A1 deletion analysis Nature structural & molecular biology High 38773334
2022 GCN2, a second nutrient-sensing kinase, converges on LARP1 to control TOP mRNA translation via two mechanisms: (1) ATF4-dependent transcriptional induction of LARP1 mRNA, and (2) GCN1-mediated recruitment of LARP1 to stalled ribosomes (GCN1 participates in a complex with LARP1 on stalled ribosomes). ChIP-seq (ATF4 binding at LARP1 locus), GCN2 knockout MEFs, co-immunoprecipitation (GCN1-LARP1 on stalled ribosomes), TOP mRNA translation assays The Journal of biological chemistry Medium 35863436
2009 Drosophila Larp exists in a physical complex with and genetically interacts with the translation regulator poly(A)-binding protein (PABP). Larp mutant-derived syncytial embryos show mitotic phenotypes including centrosome migration failure, centrosome detachment from spindle poles, multipolar spindle arrays, and cytokinetic defects. larp mutant males show meiotic defects similar to hypomorphic pAbp alleles. Co-immunoprecipitation (Larp-PABP complex), genetic epistasis (larp and pAbp double mutants), immunofluorescence (mitotic phenotype analysis) Developmental biology Medium 19631203
2008 C. elegans LARP-1 localizes to germline P bodies, attenuates Ras-MAPK signaling during oogenesis, and larp-1 null mutants have higher than normal levels of selected Ras-MAPK pathway mRNAs and proteins. larp-1 null oogenesis defects are suppressed or enhanced by down- or up-regulating Ras-MAPK pathway. LARP-1 binds RNA in vitro via both its La motif and LARP1 domain. In vitro RNA binding assays (La motif and LARP1 domain), genetic epistasis (larp-1 with Ras-MAPK pathway components), immunofluorescence (P body colocalization), mRNA/protein level analysis in larp-1 nulls RNA (New York, N.Y.) Medium 18515547
2010 C. elegans LARP-1 promotes oogenesis by repressing fem-3 mRNA. Simultaneous depletion of larp-1 and nos-3 causes germline masculinization dependent on fem-3 activity. fem-3 mRNA levels are increased in larp-1 mutants, indicating LARP-1 suppresses fem-3 expression through a distinct mechanism from NOS-3. RNAi depletion, genetic epistasis (larp-1;nos-3 double knockdown with fem-3 activity requirement), qPCR/Western blot for TRA-1 and FEM protein levels Journal of cell science Medium 20663921
2021 LARP1 and LARP4 share direct binding to poly(A) and to cytoplasmic PABP (PABPC1) through PAM2 motifs interacting with the MLLE domain of PABP. LARP1 can protect mRNA from deadenylation in a PAM2-dependent manner. The La-module of LARP1 interacts with PABP to stabilize poly(A) tails. Biochemical binding assays (PAM2-MLLE interaction), mRNA stabilization assays, co-immunoprecipitation RNA biology Medium 33522422
2023 O-GlcNAcylation of LARP1 at Ser672 by O-GlcNAc transferase (OGT) strengthens its binding to circCLNS1A and protects LARP1 from TRIM-25-mediated ubiquitination and proteolysis. LARP1 upregulation leads to DKK4 mRNA stabilization by competitively interacting with PABPC1 to prevent DKK4 mRNA from BTG2-dependent deadenylation and degradation. Co-immunoprecipitation (LARP1-circCLNS1A, LARP1-PABPC1), site-specific mutagenesis (Ser672), protein stability assays, RIP, RNA pull-down, mRNA stability assays, poly(A)-tail length assays Clinical and translational medicine Medium 37070251
2025 LARP1 interacts with the 5'UTR of EV-D68 RNA through its LAM domain, and this interaction is crucial for its antiviral function. EV-D68 protease 3Cpro cleaves LARP1 and PABPC1 to counteract LARP1-mediated inhibition of viral translation. Overexpression of LARP1 significantly inhibits EV-D68 replication. mTOR and CDK1 signaling pathways regulate LARP1's binding to viral RNA. Domain mapping (LAM domain interaction with viral 5'UTR), overexpression and siRNA knockdown with viral replication readouts, protease cleavage assays, mTOR/CDK1 pathway inhibitor experiments PLoS pathogens Medium 40294010
2024 The LARP1 PAM2 motif adopts a non-canonical single turn α-helix conformation for MLLE domain binding. Phenylalanine 496 in the PAM2 motif is essential for MLLE binding. NMR chemical shift perturbations defined the MLLE-binding segment within LARP1. NMR spectroscopy (chemical shift perturbation, heteronuclear NOE), isothermal titration calorimetry (ITC), PAM2 mutagenesis, AlphaFold3 modeling Biochemical and biophysical research communications Medium 41762867
2024 The LARP1 LaM domain shows preferential binding to poly(A) sequences with single guanine substitutions over unmodified poly(A). Crystal structures of the LARP1 LaM with six different RNA ligands, including singly guanylated sequences, define the structural basis for this selectivity. X-ray crystallography (multiple structures), isothermal titration calorimetry (ITC) RNA biology Medium 39016322
2025 Brain-specific knockout of Larp1 in mice significantly decreases brain mass, reduces neuronal density, depletes TOP mRNA levels by more than 50%, and selectively removes TOP mRNAs from synapses. Larp1-deficient mice are severely impaired in spatial learning and memory. Brain-specific conditional knockout (Cre-lox), brain mass and neuron density quantification, RNA-seq (TOP mRNA abundance), synaptic fractionation with RNA-seq, behavioral testing (spatial memory) bioRxivpreprint Medium 41278816
2026 LARP1's ribosome-binding region is part of a previously unrecognized RNA recognition motif (RRM) domain that directly interacts with its TOP-binding HEAT repeat (DM15) domain. Ribosome binding is both sufficient in vitro and required in cells for LARP1 to bind, repress, and stabilize TOP mRNAs via unfolding and remodeling of the RRM domain. RRM mutations that disrupt ribosome binding constitutively repress TOPs and compromise cell fitness. Cryo-EM (structural identification of RRM), in vitro ribosome binding assay, RRM mutagenesis, TOP mRNA repression and stability assays in cells, cell fitness/growth assays bioRxivpreprint Medium 42039457
2025 5'TOP motifs are sufficient to increase mRNA targeting to lysosomes for degradation in a LARP1-dependent manner, establishing a role for LARP1 in selective lysosomal delivery of TOP mRNAs. Lysosomal RNA profiling, LARP1 depletion with lysosomal TOP mRNA accumulation readout, reporter assays with TOP motif bioRxivpreprint Low bio_10.1101_2025.09.09.674968
2025 LARP1 overexpression alleviates angiotensin II-induced cardiac remodeling. LARP1 binds ATP2A2 (SERCA2a) mRNA and enhances its stability; ATP2A2 overexpression reverses hypertrophic and fibrotic changes in LARP1-deficient cardiomyocytes. RNA immunoprecipitation (RIP), RNA pull-down, mRNA stability assay (actinomycin D), AAV9-LARP1 overexpression in vivo, LARP1 KO mice with cardiac phenotype readouts Cell & bioscience Medium 41126333
2022 LARP1 positively modulates MYC expression by associating with the MYC 3'UTR. Antisense oligonucleotide-mediated blocking of the LARP1–MYC 3'UTR interaction reduces MYC expression. MYC reciprocally modulates LARP1 expression by targeting its enhancer, establishing a positive feedback loop. IGF2BP3 and YBX1 are identified as LARP1-interacting proteins. RIP-seq (LARP1 interactome), antisense oligonucleotide blocking assay, co-immunoprecipitation (LARP1-IGF2BP3, LARP1-YBX1), ChIP (MYC at LARP1 enhancer), mRNA stability/translation assays Cellular and molecular life sciences : CMLS Medium 35195778

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1). The Journal of biological chemistry 215 25940091
2014 Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5'TOP mRNA translation. Genes & development 210 24532714
2017 LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs. eLife 173 28650797
2017 La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs. eLife 152 28379136
2020 Global analysis of LARP1 translation targets reveals tunable and dynamic features of 5' TOP motifs. Proceedings of the National Academy of Sciences of the United States of America 134 32094190
2015 The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer. Nucleic acids research 133 26717985
2013 XRN4 and LARP1 are required for a heat-triggered mRNA decay pathway involved in plant acclimation and survival during thermal stress. Cell reports 125 24332370
2014 LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression. Oncogene 124 25531318
2010 The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration. Nucleic acids research 103 20430826
2018 La-related protein 1 (LARP1) repression of TOP mRNA translation is mediated through its cap-binding domain and controlled by an adjacent regulatory region. Nucleic acids research 102 29244122
2013 LARP1 specifically recognizes the 3' terminus of poly(A) mRNA. FEBS letters 91 23711370
2018 CircRNA circ-BANP-mediated miR-503/LARP1 signaling contributes to lung cancer progression. Biochemical and biophysical research communications 83 29969631
2021 mTORC1 promotes TOP mRNA translation through site-specific phosphorylation of LARP1. Nucleic acids research 81 33398329
2009 Drosophila Larp associates with poly(A)-binding protein and is required for male fertility and syncytial embryo development. Developmental biology 81 19631203
2020 Parallel global profiling of plant TOR dynamics reveals a conserved role for LARP1 in translation. eLife 77 33054972
2020 Controversies around the function of LARP1. RNA biology 65 32233986
2008 C. elegans La-related protein, LARP-1, localizes to germline P bodies and attenuates Ras-MAPK signaling during oogenesis. RNA (New York, N.Y.) 64 18515547
2018 LARP1 on TOP of ribosome production. Wiley interdisciplinary reviews. RNA 59 29722158
2011 Control of flowering and cell fate by LIF2, an RNA binding partner of the polycomb complex component LHP1. PloS one 54 21304947
2006 DamID, a new tool for studying plant chromatin profiling in vivo, and its use to identify putative LHP1 target loci. The Plant journal : for cell and molecular biology 42 16972870
2021 Hsa_circRNA_002144 promotes growth and metastasis of colorectal cancer through regulating miR-615-5p/LARP1/mTOR pathway. Carcinogenesis 39 33347535
2017 LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma. Oncology reports 39 29039571
2011 TFL2/LHP1 is involved in auxin biosynthesis through positive regulation of YUCCA genes. The Plant journal : for cell and molecular biology 39 21251106
2007 A Drosophila orthologue of larp protein family is required for multiple processes in male meiosis. Cell structure and function 37 17951964
2015 The role of LARP1 in translation and beyond. Wiley interdisciplinary reviews. RNA 35 25892282
2024 Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5'TOP mRNAs. Science advances 33 38363833
2021 LARP1 and LARP4: up close with PABP for mRNA 3' poly(A) protection and stabilization. RNA biology 33 33522422
2019 The LARP1 La-Module recognizes both ends of TOP mRNAs. RNA biology 33 31601159
2021 The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction. Nucleic acids research 32 33332560
2017 Disruption of an RNA-binding hinge region abolishes LHP1-mediated epigenetic repression. Genes & development 32 29212661
2019 Capturing the Mechanism Underlying TOP mRNA Binding to LARP1. Structure (London, England : 1993) 31 31676287
2021 The 40S-LARP1 complex reprograms the cellular translatome upon mTOR inhibition to preserve the protein synthetic capacity. Science advances 30 34818049
2020 The isolated La-module of LARP1 mediates 3' poly(A) protection and mRNA stabilization, dependent on its intrinsic PAM2 binding to PABPC1. RNA biology 30 33292040
2022 Structural basis of 3'-end poly(A) RNA recognition by LARP1. Nucleic acids research 29 35979957
2022 mTOR- and LARP1-dependent regulation of TOP mRNA poly(A) tail and ribosome loading. Cell reports 29 36288708
2023 Short poly(A) tails are protected from deadenylation by the LARP1-PABP complex. Nature structural & molecular biology 28 36849640
2017 LHP1 Could Act as an Activator and a Repressor of Transcription in Plants. Frontiers in plant science 25 29234344
2018 LHP1 Interacts with ATRX through Plant-Specific Domains at Specific Loci Targeted by PRC2. Molecular plant 24 29793052
2024 LARP1 binds ribosomes and TOP mRNAs in repressed complexes. The EMBO journal 22 39533057
2021 GmBTB/POZ promotes the ubiquitination and degradation of LHP1 to regulate the response of soybean to Phytophthora sojae. Communications biology 18 33742112
2020 LARP1 isoform expression in human cancer cell lines. RNA biology 16 32286153
2010 LARP-1 promotes oogenesis by repressing fem-3 in the C. elegans germline. Journal of cell science 16 20663921
2021 Downregulation of the lncRNA ASB16-AS1 Decreases LARP1 Expression and Promotes Clear Cell Renal Cell Carcinoma Progression via miR-185-5p/miR-214-3p. Frontiers in oncology 13 33680937
2020 Knockdown of KCNQ1OT1 Inhibits Proliferation, Invasion, and Drug Resistance by Regulating miR-129-5p-Mediated LARP1 in Osteosarcoma. BioMed research international 12 32953888
2024 eIF4A1 enhances LARP1-mediated translational repression during mTORC1 inhibition. Nature structural & molecular biology 11 38773334
2023 O-GlcNAcylated LARP1 positively regulated by circCLNS1A facilitates hepatoblastoma progression through DKK4/β-catenin signalling. Clinical and translational medicine 11 37070251
2023 LHP1-mediated epigenetic buffering of subgenome diversity and defense responses confers genome plasticity and adaptability in allopolyploid wheat. Nature communications 11 37985755
2022 The amino acid sensor GCN2 suppresses terminal oligopyrimidine (TOP) mRNA translation via La-related protein 1 (LARP1). The Journal of biological chemistry 11 35863436
2021 Long Non-coding RNA LINC01969 Promotes Ovarian Cancer by Regulating the miR-144-5p/LARP1 Axis as a Competing Endogenous RNA. Frontiers in cell and developmental biology 11 33614632
2024 LARP1, an RNA-binding protein, participates in ovarian cancer cell survival by regulating mitochondrial oxidative phosphorylation in response to the influence of the PI3K/mTOR pathway. Biochimica et biophysica acta. Molecular basis of disease 10 39111634
2022 Global analysis of RNA-binding proteins identifies a positive feedback loop between LARP1 and MYC that promotes tumorigenesis. Cellular and molecular life sciences : CMLS 10 35195778
2023 The LARP1 homolog Slr1p controls the stability and expression of proto-5'TOP mRNAs in fission yeast. Cell reports 8 37851576
2024 Enhanced binding of guanylated poly(A) RNA by the LaM domain of LARP1. RNA biology 7 39016322
2019 LARP1 binding to hepatitis C virus particles is correlated with intracellular retention of viral infectivity. Virus research 7 31398365
2011 Conservation and divergence of plant LHP1 protein sequences and expression patterns in angiosperms and gymnosperms. Molecular genetics and genomics : MGG 7 21416255
2025 EV-D68 cleaves LARP1 and PABPC1 by 3Cpro to redirect host mRNA translation machinery toward its genomic RNA. PLoS pathogens 6 40294010
2023 The MYC-Regulated RNA-Binding Proteins hnRNPC and LARP1 Are Drivers of Multiple Myeloma Cell Growth and Disease Progression and Negatively Predict Patient Survival. Cancers 6 38067212
2024 Proximity labeling of host factor ANXA3 in HCV infection reveals a novel LARP1 function in viral entry. The Journal of biological chemistry 5 38636657
2024 Genome-wide investigation of the LARP gene family: focus on functional identification and transcriptome profiling of ZmLARP6c1 in maize pollen. BMC plant biology 5 38684961
2024 LARP1 haploinsufficiency is associated with an autosomal dominant neurodevelopmental disorder. HGG advances 5 39182167
2023 Circ-PDZD8 promotes cell growth and glutamine metabolism in non-small cell lung cancer by enriching LARP1 via sequestering miR-330-5p. Thoracic cancer 5 37349870
2023 LARP1 senses free ribosomes to coordinate supply and demand of ribosomal proteins. bioRxiv : the preprint server for biology 5 37961604
2022 Long non-coding RNA LINC01270 is an onco-promotor in lung adenocarcinoma by upregulating LARP1 via sponging miR-326. Bioengineered 5 36694453
2024 Overexpression of LAR1 Suppresses Anthocyanin Biosynthesis by Enhancing Catechin Competition Leading to Promotion of Proanthocyanidin Pathway in Spine Grape (Vitis davidii) Cells. International journal of molecular sciences 4 39596158
2023 LARP-assisted synthesis of CsBi3I10 perovskite for efficient lead-free solar cells. RSC advances 4 37006347
2025 Targeting LARP1 to mitigate aging in lens epithelial cells: mechanistic insights into mitochondrial dysfunction. Experimental eye research 3 40818631
2025 Insights into key kinase regulatory network of LARP1 based on co-occurring phosphorylation events. Biochimica et biophysica acta. Proteins and proteomics 3 41109578
2024 LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior. Open life sciences 3 38283117
2022 Identification and molecular evolution of the La and LARP genes in 16 plant species: A focus on the Gossypium hirsutum. International journal of biological macromolecules 3 36306895
2021 The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass. Scientific reports 3 33483593
2025 Telocinobufagin suppresses malignant metastasis of undifferentiated thyroid carcinoma via modulation of the LARP1-mTOR pathway. The Kaohsiung journal of medical sciences 2 39786317
2025 LARP1 acts as a key mediator in preventing angiotensin II-induced cardiac dysfunction and fibrosis. Cell & bioscience 2 41126333
2025 Conserved Functions of LARP1 Proteins in Eukaryotes. Wiley interdisciplinary reviews. RNA 2 41287456
2024 The methyltransferase KIAA1429 potentiates cervical cancer tumorigenesis via modulating LARP1 mRNA m6A modification and stability. Histology and histopathology 2 39558874
2024 Comparative analysis of the LARP1 C-terminal DM15 region through Coelomate evolution. PloS one 1 39190712
2019 Gene cloning, expression pattern analysis, and subcellular localization of LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) homologs in chrysanthemum (Chrysanthemum morifolium Ramat.). Cellular and molecular biology (Noisy-le-Grand, France) 1 30942153
2019 C-lection by the DM15 Motif Gets LARP1 to the TOP. Structure (London, England : 1993) 1 31801095
2026 The divergent LARP1 PAM2 motif adopts a non-canonical conformation for MLLE binding. Biochemical and biophysical research communications 0 41762867
2026 Deficiency of LARP1 Impairs Spermatogenesis and Leads to Male Subfertility in Mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41934340
2026 The LARP1 RRM functions as a ribosome responsive regulator of TOP mRNAs. bioRxiv : the preprint server for biology 0 42039457
2026 Multi-omics analysis reveals LARP1 as a key integrator of translation and metabolism in AML. Oncogenesis 0 42143046
2025 Larp1 supports brain growth and spatial memory via post-transcriptional control of the translation machinery. bioRxiv : the preprint server for biology 0 41278816
2025 LAR1 promotes breast carcinogenesis by activating NF-κB signaling pathway through binding and enhancing APOC1 expression. iScience 0 41623496

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