Table 1 Biological functions and role of m7G methyltransferases in human diseases

Cardiovascular diseases

Heart failure (HF)

METTL1

METTL1 drives cardiac hypertrophy by regulating SRSF9-mediated splicing of NFATc4, serving as a critical modulator of myocardial hypertrophy and offering a novel therapeutic target for HF

[61]

Peripheral arterial disease (PAD)

METTL1

METTL1 promotes post-ischaemic angiogenesis by enhancing the translation of VEGFA mRNA, presenting significant therapeutic potential for PAD

[74]

Developmental and neurological disorders

Teratoma

METTL1

METTL1-mediated m7G methylation maintains pluripotency in human stem cells, limits mesodermal differentiation, and restricts vascular development. METTL1 silencing alters the global m7G profile in human-induced pluripotent stem cells, reduces the translation efficiency of stem cell markers, slows the cell cycle, and skews differentiation toward mesodermal fates while inhibiting neuroectodermal differentiation in vitro and in vivo

[75]

Microcephalic primordial dwarfism

WDR4

Mutations in WDR4 disrupt tRNA m7G46 methylation, causing a unique form of microcephalic primordial dwarfism. Patients with a WDR4-R170L missense mutation exhibit defective m7G levels on tRNA, implicating additional human disease-related modification genes

[76]

Down syndrome

WDR4

WDR4 has been identified as a candidate gene for Down syndrome. Overexpression of Wdr4 in Ts1Yah mouse models enhances learning and memory in the hippocampus

[77]

Alzheimer’s disease (AD)

METTL1

METTL1 expression is downregulated in excitatory neurons, astrocytes, and microglia within the cortex and hippocampus in AD models

[78]

Inflammatory-related diseases

Pneumonia

TrmB

Deletion of the m7G tRNA methyltransferase TrmB significantly alleviates lung infections caused by the pathogen Acinetobacter baumannii in mice

[79]

Metabolic-related diseases

Osteoarthritis

METTL1

Elevated METTL1 expression and m7G levels in osteoarthritis chondrocytes upregulate mt-tRF3b-LeuTAA expression, exacerbating chondrocyte degeneration and inducing osteoarthritis progression

[80]

Tumours

Acute myeloid leukaemia

METTL1/WDR4

METTL1 knockdown reduces tRNA m7G modification, destabilizes tRNA, increases tsRNA production, and disrupts global translation efficiency in AML cells

[72]

Intrahepatic cholangiocarcinoma

METTL1

METTL1 knockout inhibits the PI3K/AKT/mTOR signaling pathway, reducing proliferation and lymphatic metastasis in ICC mouse models

[81]

Prostate cancer

METTL1

METTL1 depletion disrupts m7G tRNA methylation, promoting 5' tsRNAs that enhance tumor growth suppression, the interferon pathway, and immune effectors

[82]