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Results for “TRMT61A”

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4 recordsLinked to original sources
PubMed2026

Translational reprogramming of TGF-β signaling via TRMT61A-mediated tRNA m1A drives prostatic fibrosis and hyperplasia.

Dysregulation of the epitranscriptomic landscape is closely linked to pathological proliferation, but its specific role in benign prostatic hyperplasia (BPH) remains unclear. Here, we identify the tRNA methyltransferase TRMT61A as a critical driver of BPH progression. We found that TRMT61A and global N1-methyladenosine (m1A) levels are aberrantly upregulated in human BPH tissues. Functionally, TRMT61A knockdown potently suppresses prostate cell proliferation and reduces stromal fibrosis, inducing G1 cell cycle arrest and reversing pathological remodeling both in vitro and in vivo. By integrating ribosome profiling (Ribo-seq) and tRNA-seq, we observed that TRMT61A drives translational reprogramming. TRMT61A preserves the stability of specific tRNA isoacceptors (e.g., tRNA-Leu-CAA), which is required for the efficient decoding of mRNAs containing m1A-dependent codons. Consequently, TRMT61A selectively promotes the translational elongation of the key receptor TGFβR1. This amplifies downstream TGF-β/SMAD signaling and drives epithelial-mesenchymal transition (EMT) without affecting mRNA transcription. In summary, our study reveals how TRMT61A drives BPH progression through TGFβR1 translation, highlighting the therapeutic potential of targeting epitranscriptomic pathways to reverse prostatic hyperplasia and fibrosis.

Male↗
PubMed2026

tRNA m1A modification orchestrates STING translation in macrophages to enhance antitumor immunity and CAR-macrophage immunotherapy.

Tumor-associated macrophages (TAMs) play crucial roles in tumor progression. However, the mechanisms underlying the posttranscriptional regulation of TAMs remain largely unknown. Here, we demonstrated that Trmt61a, the "writer" enzyme of tRNA N1-methyladenosine (m1A) modification, is highly expressed in proinflammatory macrophages in tumor microenvironment. We generated conditional knockout (KO) mice for Trmt61a and observed that Trmt61a deletion in macrophages significantly promoted tumor growth. Mechanistically, we identified that m1A maintains the translation of STING, enhances STING-TBK1-IFN-β signaling in macrophages and therefore suppresses tumor cell growth. We further generated TRMT61A-overexpressing human iPSC-derived CAR-macrophage and demonstrated that human TRMT61A effectively promoted antitumor CAR-macrophage therapy in vivo. Collectively, our findings reveal a novel regulatory mechanism of tRNA m1A modification in macrophages, highlighting the antitumor therapeutic potential of targeting tRNA m1A modification in macrophages.

Animals↗
PubMed2025

m1A methylase TRMT6 promotes neuroblastoma development by demethylating SST mRNA in an m1A/YTHDF2-dependent manner.

BACKGROUND: m1A, a prevalent RNA modification found in various RNA species, has recently been reported to modulate cancer progression. However, its effects on neuroblastoma remain uninvestigated. METHODS: The PCAT database was utilized to analyze the mRNA levels and survival probabilities of m1A regulator genes (TRMT6, TRMT61A, ALKBH1, and ALKBH3) in neuroblastoma patients. Silencing and recovery of TRMT6 were employed to investigate its role in neuroblastoma in vitro and in vivo. m1A-seq and RIP-qPCR were performed to identify and confirm the downstream targets of TRMT6. Additionally, Actinomycin D treatment was administered to assess mRNA stability. RESULTS: m1A transmethylase TRMT6 expression was significantly elevated in high-risk and late-stage neuroblastoma patients. Functionally, TRMT6 promotes the malignancy of neuroblastoma cells in vitro and promotes tumor growth and metastasis in vivo. Mechanistically, TRMT6 reduces SST mRNA levels by inhibiting its stability in an m1A-YTHDF2-dependent manner, thereby promoting the development of neuroblastoma. Furthermore, SST analog octreotide suppresses neuroblastoma cell malignancy, tumor growth, and metastasis. CONCLUSIONS: TRMT6 mediates m1A modification of SST to promote neuroblastoma progression, suggesting that targeting TRMT6 may be a novel potential therapeutic approach for treating neuroblastoma.

Neuroblastoma↗
PubMed2025

The relationship between vitamin D levels and depression: a genetically informed study.

BACKGROUND: Low vitamin D (vitD) levels are consistently associated with an increased risk of depression. However, the biological mechanisms underlying this relationship and potential shared genetic overlap remain elusive. METHODS: We investigated the genetic overlap and causal relationships between depression (N = 589,356) and vitD levels (N = 417,580) using genome-wide association study (GWAS) summary statistics. We performed genome-wide and local genetic correlation analyses, followed by quantification of polygenic overlap variants. Shared genetic loci were identified and mapped to genes, which were further analyzed through gene expression and lifespan brain expression trajectory analyses. Bidirectional causal relationships were examined using multiple Mendelian randomization approaches. RESULTS: We observed significant negative genetic correlations (rg = -0.079) and identified genetic overlap (N = 410 variants). Genes mapped to the 13 shared loci showed opposing expression patterns. Tissue- and cell-specific functional enrichment analyses revealed significant signals related to brain development, with distinct patterns emerging between fetal development and adulthood. Shared genes (TRMT61A, ITIH4, RASGRP1, CTNND1, HERC1, IP6K1, FURIN ESR1, ZMYND and GRM5) exhibited notable expression variation in the brian throughout the lifespan, aligning with functional enrichment findings. CONCLUSIONS: Our findings elucidate the shared biological mechanisms underlying the relationship between vitD and depression, suggesting that vitD play an important role in the development of depression through altered early neurodevelopmental processes.

Humans↗