Affinage

TMA16

Translation machinery-associated protein 16 · UniProt Q96EY4

Round 2 corrected
Length
203 aa
Mass
23.9 kDa
Annotated
2026-04-28
34 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TMA16 is a ribosome assembly factor that occupies a specific position between the 5S rRNA and the P0 stalk in human pre-60S ribosomal particles at the nuclear export checkpoint stage, as determined by cryo-EM structural analysis of NMD3-associated intermediates (PMID:32669547). In yeast, TMA16 mRNA abundance is controlled by P-body-mediated degradation via Lsm1, and loss of this regulation during DNA replication stress leads to toxic TMA16 mRNA accumulation (PMID:28916784).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2017 Medium

    Establishing that TMA16 expression must be tightly regulated: yeast genetic analysis showed that P-body-mediated mRNA turnover prevents toxic accumulation of TMA16 mRNA during replication stress, revealing the gene as a dosage-sensitive factor.

    Evidence Genetic screen and mRNA measurements in yeast lsm1Δ mutants under hydroxyurea stress

    PMID:28916784

    Open questions at the time
    • Mechanism of toxicity from TMA16 overaccumulation is unknown
    • Whether protein-level (not just mRNA-level) regulation occurs is unresolved
    • Relevance to mammalian cells not tested
  2. 2020 High

    Defining TMA16's structural role in ribosome biogenesis: cryo-EM localized TMA16 between the 5S rRNA and P0 stalk on human pre-60S particles at the nuclear export checkpoint, establishing it as a bona fide assembly factor at a defined maturation step.

    Evidence Cryo-EM of human pre-60S particles purified via NMD3, resolving multiple assembly intermediates

    PMID:32669547

    Open questions at the time
    • Functional consequence of TMA16 depletion on 60S maturation not tested
    • No biochemical reconstitution of TMA16 binding to the pre-60S particle
    • Timing and mechanism of TMA16 release from the maturing 60S subunit are unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether TMA16 plays an active catalytic or structural role on the pre-60S particle, what triggers its recruitment and release, and whether its dosage sensitivity in yeast reflects a conserved quality-control mechanism in human ribosome biogenesis.
  • No loss-of-function studies in human cells
  • No binding partners or interaction surfaces mapped at residue resolution
  • Relationship between mRNA-level regulation (yeast) and structural role (human) not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 1
Localization
GO:0005840 ribosome 1
Pathway
R-HSA-392499 Metabolism of proteins 1
Partners
NMD3
Complex memberships
pre-60S ribosomal particle

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 TMA16 was localized by cryo-EM structural analysis to a position between the 5S rRNA and the P0 stalk in human pre-60S ribosomal particles at assembly stages immediately before and after nuclear export, identifying it as a previously uncharacterized assembly factor present at this specific checkpoint stage of ribosome biogenesis. Cryo-EM structural determination of human pre-60S particles isolated via the nuclear export factor NMD3 Nature Communications High 32669547
2017 In yeast, TMA16 mRNA accumulates to toxic levels during DNA replication stress when the P-body protein Lsm1 is absent, indicating that P-body-mediated degradation/storage normally controls TMA16 mRNA abundance to prevent toxicity during the replication stress response. Genetic screen and mRNA abundance measurements in yeast P-body mutants (lsm1Δ) under hydroxyurea-induced replication stress Nature Communications Medium 28916784

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2011 Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. The Journal of biological chemistry 131 21832049
2009 Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays. Molecular systems biology 129 19953087
2023 The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation. Science (New York, N.Y.) 117 37616343
2011 Proteomic characterization of the human sperm nucleus. Proteomics 116 21630459
2021 Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry. Proceedings of the National Academy of Sciences of the United States of America 113 34349018
2021 FBW7 suppresses ovarian cancer development by targeting the N6-methyladenosine binding protein YTHDF2. Molecular cancer 106 33658012
2022 EZH2 depletion potentiates MYC degradation inhibiting neuroblastoma and small cell carcinoma tumor formation. Nature communications 99 35013218
2017 Cell cycle-dependent phosphorylation regulates RECQL4 pathway choice and ubiquitination in DNA double-strand break repair. Nature communications 89 29229926
2014 Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation. Cell reports 80 24981860
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2019 The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis. Nature communications 74 31586073
2022 Transcription factor protein interactomes reveal genetic determinants in heart disease. Cell 67 35182466
2018 RNA-binding proteins with basic-acidic dipeptide (BAD) domains self-assemble and aggregate in Alzheimer's disease. The Journal of biological chemistry 65 29802200
2021 Loss of TRIM31 promotes breast cancer progression through regulating K48- and K63-linked ubiquitination of p53. Cell death & disease 64 34650049
2022 MYC multimers shield stalled replication forks from RNA polymerase. Nature 63 36424410
2020 Structural snapshots of human pre-60S ribosomal particles before and after nuclear export. Nature communications 60 32669547
2017 P-body proteins regulate transcriptional rewiring to promote DNA replication stress resistance. Nature communications 32 28916784
2015 Genome-wide association study for the interaction between BMR and BMI in obese Korean women including overweight. Nutrition research and practice 24 26865924
2025 Characterization of methylation profile in biofluid cell-free DNA and identification of differentially methylated genes for phenotypic representations in Parkinson's disease. Clinical neurology and neurosurgery 1 40527220