# Psmd13, a proteasome regulatory subunit identified in miR-29a regulation during neuronal differentiation **Authors:** Diji Kuriakose, Grant Morahan, Zhi-cheng Xiao PMC · DOI: 10.1371/journal.pone.0341845 · PLOS One · 2026-02-24 ## TL;DR This study identifies Psmd13 as a key regulator of miR-29a during neuronal differentiation, linking it to neurodevelopmental processes. ## Contribution The novel contribution is identifying Psmd13 as an upstream regulator of miR-29a in neuronal differentiation through genetic and functional analyses. ## Key findings - Psmd13 knockdown in mNPCs enhances neuronal differentiation and upregulates miR-29a in undifferentiated cells. - Psmd13 and Dicer co-occupy genomic loci, including miR-29a, suggesting a role in transcriptional regulation. - Proteasome inhibition reduces Psmd13 and Dicer levels, suppressing miR-29a and impairing neuronal differentiation. ## Abstract miR-29a is essential for neuronal development and implicated in neurodegenerative disease, yet its upstream regulation remains unclear. Using genetically diverse Collaborative Cross (CC) mice, we performed expression profiling and QTL mapping, identifying a strong locus on chromosome 7. Among ten candidates, Psmd13 emerged as a key regulator. RNAi-mediated Psmd13 knockdown in mouse neural precursor cells (mNPCs) enhanced neuronal differentiation, with miR-29a upregulated in the undifferentiated state but reduced upon differentiation. Co-immunoprecipitation suggested an association between Psmd13 and Dicer, correlating with state-dependent changes in miR-29a levels. ChIP-seq revealed overlapping chromatin occupancy of Psmd13 and Dicer at several genomic loci, including miR-29a, consistent with—but not directly demonstrating—a role in chromatin accessibility and transcriptional control. Proteasome inhibition with MG132 lowered Psmd13 and Dicer, suppressed miR-29a, and impaired neuronal differentiation. Together, these findings suggest that differentiation dynamically regulates miR-29a expression through Psmd13–Dicer interactions, supporting a model in which Psmd13 acts as an upstream modulator of miRNA control and neurodevelopmental homeostasis. ## Linked entities - **Genes:** PSMD13 (proteasome 26S subunit, non-ATPase 13) [NCBI Gene 5719], MIR29A (microRNA 29a) [NCBI Gene 407021], DICER1 (dicer 1, ribonuclease III) [NCBI Gene 23405] - **Chemicals:** MG132 (PubChem CID 462382) - **Species:** Mus musculus (taxon 10090) ## Full-text entities - **Genes:** Lmntd2 (lamin tail domain containing 2) [NCBI Gene 72000] {aka 1600016N20Rik}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, Psmd13 (proteasome (prosome, macropain) 26S subunit, non-ATPase, 13) [NCBI Gene 23997] {aka S11}, Rb1 (RB transcriptional corepressor 1) [NCBI Gene 19645] {aka Rb, Rb-1, p110-RB1, pRb, pp105}, Mul1 (mitochondrial ubiquitin ligase activator of NFKB 1) [NCBI Gene 68350] {aka 0610009K11Rik, Gide, Tnrip-1}, MIR29A (microRNA 29a) [NCBI Gene 407021] {aka MIRN29, MIRN29A, hsa-mir-29, hsa-mir-29a, miRNA29A, mir-29a}, Caly (calcyon neuron-specific vesicular protein) [NCBI Gene 68566] {aka 0710001P07Rik, 1110004A22Rik, Calcyon, Drd1ip}, Zfp281 (zinc finger protein 281) [NCBI Gene 226442] {aka Znf281}, Ago2 (argonaute RISC catalytic subunit 2) [NCBI Gene 239528] {aka 1110029L17Rik, 2310051F07Rik, Eif2c2, Gerp95, Gm10365, mKIAA4215}, Shank2 (SH3 and multiple ankyrin repeat domains 2) [NCBI Gene 210274] {aka ProSAP1, mKIAA1022}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, DCX (doublecortin) [NCBI Gene 1641] {aka DBCN, DC, LISX, SCLH, XLIS}, PSMD13 (proteasome 26S subunit, non-ATPase 13) [NCBI Gene 5719] {aka HSPC027, Rpn9, S11, p40.5}, Zfp14 (zinc finger protein 14) [NCBI Gene 243906] {aka 4732429I09Rik, Krox-9, Zfp-14, mKIAA1559}, Setdb1 (SET domain, bifurcated 1) [NCBI Gene 84505] {aka ESET, KMT1E, mKIAA0067}, Ap2a2 (adaptor-related protein complex 2, alpha 2 subunit) [NCBI Gene 11772] {aka 2410074K14Rik, Adtab, L25}, Syt8 (synaptotagmin VIII) [NCBI Gene 55925], Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], Nap1l4 (nucleosome assembly protein 1-like 4) [NCBI Gene 17955] {aka 2810410H14Rik, D7Wsu30e, Nap2}, Egf (epidermal growth factor) [NCBI Gene 13645], Cttn (cortactin) [NCBI Gene 13043] {aka 1110020L01Rik, Ems1}, Prdm9 (PR domain containing 9) [NCBI Gene 213389] {aka Dsbc1, G1-419-29, Meisetz, PRDM9-B, Rcr1, repro7}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Trim28 (tripartite motif-containing 28) [NCBI Gene 21849] {aka KAP-1, KRIP-1, MommeD9, Tif1b, Tif1beta}, Tubb3 (tubulin, beta 3 class III) [NCBI Gene 22152] {aka 3200002H15Rik, M(beta)3, M(beta)6}, Hsp86-ps2 (heat shock protein 86, pseudogene 2) [NCBI Gene 111042] {aka 86kDa, Hsp86-3, Hsp90}, Dnah8 (dynein, axonemal, heavy chain 8) [NCBI Gene 13417] {aka ATPase, Dnahc8, Hst6.7b, P1-Loop}, Mdm2 (MDM2 proto-oncogene) [NCBI Gene 17246] {aka 1700007J15Rik, Mdm-2}, Rplp2 (ribosomal protein lateral stalk subunit P2) [NCBI Gene 67186] {aka 2700049I22Rik}, Psmd14 (proteasome (prosome, macropain) 26S subunit, non-ATPase, 14) [NCBI Gene 59029] {aka 2610312C03Rik, 3200001M20Rik, Pad1, Poh1, rpm11}, Map2 (microtubule-associated protein 2) [NCBI Gene 17756] {aka G1-397-34, MAP-2, Mtap-2, Mtap2, repro4}, Drosha (drosha, ribonuclease type III) [NCBI Gene 14000] {aka 1110013A17Rik, Etohi2, Rn3, Rnasen}, Igh-V7183 (immunoglobulin heavy chain (V7183 family)) [NCBI Gene 16059] {aka B9-scFv, IgG, IgH, IgVH1(VSG), VH7183, VI24H}, Mir29a (microRNA 29a) [NCBI Gene 387222] {aka Mirn29a, mir-29a, mmu-mir-29a}, Mir191 (microRNA 191) [NCBI Gene 387186] {aka Mirn191, mir-191, mmu-mir-191} - **Diseases:** neurological disorders (MESH:D009461), NPC (MESH:D052556), cognitive decline (MESH:D003072), gait disturbances (MESH:D020233), muscle weakness (MESH:D018908), Huntington's diseases (MESH:D006816), cancer (MESH:D009369), mNPCs (MESH:D054218), Alzheimer's (MESH:D000544), cardiovascular disorders (MESH:D002318), neuroinflammation (MESH:D000090862), weight loss (MESH:D015431), toxicity (MESH:D064420), Neurodegenerative disorders (MESH:D019636), Parkinson's disease (MESH:D010300), MCAO (MESH:D020244), neurological damage (MESH:D020196) - **Chemicals:** SDS (MESH:D012967), LiCl (MESH:D018021), PLO (MESH:C008973), glutamate (MESH:D018698), HCl (MESH:D006851), Tween20 (MESH:D011136), PBS (MESH:D007854), Laemmli buffer (MESH:C088816), Alexa Fluor 546 (MESH:C481052), ICE (MESH:D007053), glycine (MESH:D005998), formaldehyde (MESH:D005557), GlutaMAX (MESH:C054122), DAPI (MESH:C007293), DMSO (MESH:D004121), CO2 (MESH:D002245), polystyrene (MESH:D011137), TBS (MESH:D013725), MG132 (MESH:C072553), paraformaldehyde (MESH:C003043), EDTA (MESH:D004492), F12 (MESH:C007782), NP-40 (MESH:C010615), lipofectamine (MESH:C086724), Streptomycin (MESH:D013307), epoxy (MESH:D004853), Triton X-100 (MESH:D017830), sodium deoxycholate (MESH:D003840), NaCl (MESH:D012965), 10mMTris-HCl (-), Penicillin (MESH:D010406), HEPES (MESH:D006531), salt (MESH:D012492) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606] - **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12931756/full.md ## Figures 7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12931756/full.md ## References 44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12931756/full.md --- Source: https://tomesphere.com/paper/PMC12931756