| Annotated protein: | Poly(A) RNA polymerase GLD2 (EC 2.7.7.19) (PAP-associated domain-containing protein 4) (Terminal nucleotidyltransferase 2). Gene symbol: TENT2. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q5U315 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ TENT2 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of translation at postsynapse (GO:0140245) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Udagawa T, et al. "Bidirectional control of mRNA translation and synaptic plasticity by the cytoplasmic polyadenylation complex" Mol Cell. 2012 Jul 27;47(2):253-66 PMID:22727665 |
| Figure(s): | Fig.5, 6 |
| Annotation description: | [Fig.2: "Gld2 regulates basal and NMDA-induced dendritic poly(A)" - "NMDA treatment (100 nM, 30 seconds) increased dendritic oligo(dT) FISH intensity by 55% in distal regions as compared to control (Figure 2B), which was abrogated by the NMDAR antagonist APV (data not shown). NMDA did not affect dendritic αCaMKII mRNA levels (Figure 2B,S2B), indicating negligible transcript transport to distal dendrites during the brief stimulation. To determine if dendritic polyadenylation was sensitive to Gld2, neurons were transduced with lentiviruses expressing Gld2 shRNA or a control (Figure S5). Depletion of Gld2 reduced dendritic oligo(dT) FISH signals relative to controls (Figure 2C,D), indicating that this enzyme regulates dendritic polyadenylation."] [Fig.4: "Identification of mRNAs whose polyadenylation is controlled by Gld2" - "The data presented above imply that Gld2 controls dendritic polyadenylation and translation of specific mRNAs. To identify them, RNA was extracted from hippocampal neurons transduced with Gld2 shRNA-expressing or control lentivirus...Twenty-seven of these mRNAs have been implicated in synaptic plasticity and/or nervous system disorders; five were selected and the microarray data were validated by qRTPCR (Figure 4C). HuD (RNA binding protein) and Neto2 (kainate receptor modulator) mRNAs were reduced in the total and poly(A) RNA fractions following Gld2 knockdown, suggesting that they became unstable or their transcription was indirectly reduced upon Gld2 depletion. NR2A (NMDAR subunit) and Ago3 (Piwi protein) mRNAs were reduced only in the poly(A) RNA fraction, suggesting that their poly(A) tails were shortened by Gld2 depletion without affecting stability..."] Fig.5: "Bidirectional control of NR2A protein expression by Gld2 and Ngd" - "Upon Gld2 knockdown in hippocampal neurons, HuD and NR2A protein levels decreased by 27% and 31%, respectively (neither tubulin nor HuR was significantly affected) (Figure 5A). Conversely, depletion of Ngd, a translational repressor that inhibits eIF4F assembly (Jung et al. 2006), resulted in a 40% increase in NR2A (HuD was not measured; note that although tubulin was unaffected, the NMDAR subunit NR1 increased by ~20%) (Figure 5B). To determine if this regulation occurs in dendrites, we performed immunocytochemistry for NR2A following depletion of Gld2 or Ngd. While NR1 signal was not significantly altered, depletion of Gld2 reduced dendritic NR2A by ~20% and depletion of Ngd increased it by 30% (Figure 5C,D)." Fig.6: "NMDA induces Gld2-dependent polyadenylation and translation of NR2A mRNA" [Fig.7: "shRNA-mediated knockdown of Gld2 and Ngd impair LTP at medial perforant pathway to DG granule cell synapses"] |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA |
| Evidence tracking, Experiment Assay: | Confocal Western blot |
| Annotator(s): | Pim van Nierop (ORCID:0000-0003-0593-3443) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| SynGO annotation ID: | 3873 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |