Role of RNA-binding proteins in exercise-induced mRNA regulation: Unveiling biomarkers and therapeutic targets for schizophrenia

Table 1 Mechanisms of RNA binding protein-regulated mRNA stability and translation and exercise regulation in schizophrenia

Aspects	Key RBPs	Description	Functions and effects	Ref.
Abnormal mRNA stability	TDP-43, FUS	Research centers on the pathological changes in RBPs related to mRNA degradation and stability, such as TDP-43 and FUS, in neurons and glial cells of schizophrenia patients, possibly accelerating specific mRNA degradation	Impaired mRNA stability alters critical gene expression, exacerbating schizophrenia pathogenesis	[71]
Abnormal translation regulation	FMRP, CPEB	Abnormal mRNA translation in schizophrenia is often linked to RBP dysfunction, particularly the roles of FMRP and CPEB in synaptic translation regulation	Alters synaptic structure and function, regulating neural plasticity; abnormalities may contribute to synaptic network disruption	[72]
Effects on neurodevelopment and neurodegeneration	TDP-43, FMRP, CPEB	Abnormal mRNA stability and translation may disrupt neurodevelopmental processes, shaping neuronal connectivity and information processing, thus aggravating schizophrenia symptoms	Impacts synapse formation and pruning in the cortex and hippocampus, damaging neural networks	[77]
RBPs and synaptic function	FMRP, CPEB	Decreased FMRP expression in the brains of schizophrenia patients may contribute to synaptic dysfunction, impacting learning and memory. CPEB plays a crucial role in post-synaptic translation regulation	Abnormal expression linked to impaired post-synaptic translation regulation, shaping learning and memory capacity	[37]
RBPs and neural network remodeling	RBFOX1	RBFOX1 plays a key role in synapse formation and neural connectivity regulation; its dysfunction may contribute to abnormal network connections, causing cognitive impairment	Dysfunction leads to abnormal neural network connections, shaping cognitive function	[76]
RBPs and inflammatory response	HuR	HuR regulates the intensity and duration of immune responses by stabilizing and controlling mRNA expression of inflammation-related genes; abnormalities may contribute to excessive immune activation, worsening neuroinflammation	Plays a role in regulating inflammation gene expression; abnormalities may worsen neuroinflammation	[77]
Exercise impact on mRNA translation and stability	HuR, FMRP	Exercise substantially increases the expression of RBPs such as HuR and FMRP, helping regulate mRNA translation in synaptic plasticity and neurodevelopment	Improves synaptic function impaired by abnormal mRNA translation and stability	[81]
Exercise regulation of neurodevelopment and immune genes	BDNF, IL-6	Exercise regulates gene expression related to neurodevelopment and immune response, impacting mRNA stability and translation efficiency, which may help alleviate schizophrenia symptoms	Improves neurodevelopment and immune response, likely alleviating schizophrenia symptoms	[83]
Exercise’s role in synaptic plasticity and neural network restoration	FMRP, TDP-43	Exercise enhances synaptic plasticity, axonal transport, and neural network remodeling through RBPs like FMRP and TDP-43, restoring normal neural network function	Enhances functional recovery of neural networks, enhancing connectivity and plasticity	[53]

RBPs: RNA binding proteins; FMRP: Fragile X mental retardation protein; TDP-43: TAR DNA-binding protein 43; FUS: Fused in sarcoma; CPEB: Cytoplasmic polyadenylation element-binding protein; RBFOX1: RNA binding fox-1 homolog; HuR: Human antigen R; BDNF: Brain-derived neurotrophic factor; IL-6: Interleukin-6.

Table 2 RNA binding protein as biomarkers and therapeutic targets in schizophrenia

Biomarker	Mechanism of action	Therapeutic target	Ref.
FMRP	Downregulation of FMRP is associated with synaptic dysfunction, likely impacting cognitive deficits	Improve cognitive ability by restoring normal FMRP function to treat cognitive impairments	[37]
TDP-43	Excessive aggregation of TDP-43 is linked to neurodegeneration and impaired synaptic remodeling	Target TDP-43 aggregation to slow neurodegenerative changes	[82]
RBFOX1	Downregulation of RBFOX1 is associated with abnormalities in neurodevelopment and synaptic function	Use gene therapy to reinstate RBFOX1 function and improve cognitive deficits	[83]
CPEB	CPEB performs a key role in synaptic plasticity and neurodevelopment	Regulate CPEB expression through RNA interference to improve synaptic function and neuroplasticity	[84]

FMRP: Fragile X mental retardation protein; TDP-43: TAR DNA-binding protein 43; RBFOX1: RNA binding fox-1 homolog; CPEB: Cytoplasmic polyadenylation element-binding protein.