ArticleMolecular and cellular biology2011
La-related protein 4 binds poly(A), interacts with the poly(A)-binding protein MLLE domain via a variant PAM2w motif, and can promote mRNA stability.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 113 citations in OpenAlex.
- Characterizing highly conserved fragments in 3'UTRs via statistical and transfer learning approaches.NAR genomics and bioinformatics · 2026Article
- Inhibition of LARP4-mediated quiescence exit of naive CD4Nature biomedical engineering · 2026Article
- Designing 5' UTR sequences improves the capacity of mRNA therapeutics in preclinical models of aging and obesity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Vesicle-coupled mRNA transport and translation govern intracellular organelle networking.EMBO reports · 2026Review
- LARP4-mediated hypertranslation drives T cell dysfunction in tumors.Nature immunology · 2025Article
- Key RNA-binding domains in the La protein establish tRNA modification levels in Trypanosoma brucei.Nucleic acids research · 2025Article
- The short conserved region-2 of LARP4 interacts with ribosome-associated RACK1 and promotes translation.Nucleic acids research · 2025Article
- The short conserved region-2 of LARP4 interacts with ribosome-associated RACK1 and promotes translation.bioRxiv : the preprint server for biology · 2024Article
- Systematic identification of post-transcriptional regulatory modules.Nature communications · 2024Article
- Review
- Article
- The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis.iScience · 2024Article
- Detecting differential transcript usage in complex diseases with SPIT.Cell reports methods · 2024Article
- LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function.RNA (New York, N.Y.) · 2024Article
- Regulatory features aid interpretation of 3'UTR variants.American journal of human genetics · 2024Article
- Article
- La-related protein 4 is enriched in vaccinia virus factories and is required for efficient viral replication in primary human fibroblasts.Microbiology spectrum · 2023Article
- Complementary analysis of proteome-wide proteomics reveals changes in RNA binding protein-profiles during prostate cancer progression.Cancer reports (Hoboken, N.J.) · 2023Article
- RNA-Protein Interactome at the Hepatitis E Virus Internal Ribosome Entry Site.Microbiology spectrum · 2023Article
- Detecting differential transcript usage in complex diseases with SPIT.bioRxiv : the preprint server for biology · 2023Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
The conserved RNA binding protein La recognizes UUU-3'OH on its small nuclear RNA ligands and stabilizes them against 3'-end-mediated decay. We report that newly described La-related protein 4 (LARP4) is a factor that can bind poly(A) RNA and interact with poly(A) binding protein (PABP). Yeast two-hybrid analysis and reciprocal immunoprecipitations (IPs) from HeLa cells revealed that LARP4 interacts with RACK1, a 40S ribosome- and mRNA-associated protein. LARP4 cosediments with 40S ribosome subunits and polyribosomes, and its knockdown decreases translation. Mutagenesis of the RNA binding or PABP interaction motifs decrease LARP4 association with polysomes. Several translation and mRNA metabolism-related proteins use a PAM2 sequence containing a critical invariant phenylalanine to make direct contact with the MLLE domain of PABP, and their competition for the MLLE is thought to regulate mRNA homeostasis. Unlike all ∼150 previously analyzed PAM2 sequences, LARP4 contains a variant PAM2 (PAM2w) with tryptophan in place of the phenylalanine. Binding and nuclear magnetic resonance (NMR) studies have shown that a peptide representing LARP4 PAM2w interacts with the MLLE of PABP within the affinity range measured for other PAM2 motif peptides. A cocrystal of PABC bound to LARP4 PAM2w shows tryptophan in the pocket in PABC-MLLE otherwise occupied by phenylalanine. We present evidence that LARP4 expression stimulates luciferase reporter activity by promoting mRNA stability, as shown by mRNA decay analysis of luciferase and cellular mRNAs. We propose that LARP4 activity is integrated with other PAM2 protein activities by PABP as part of mRNA homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.