RBM10 (RNA Binding Motif Protein 10) is a nuclear RNA binding protein that plays critical roles in alternative splicing, gene expression regulation, and neuronal cell survival. Originally identified as a tumor suppressor in lung adenocarcinoma, RBM10 has emerged as an important player in neurodevelopment and neurodegenerative disease processes. [@inoue2021] The protein is part of the RBM family, which includes RBM5, RBM6, and other RNA-binding proteins that regulate post-transcriptional gene expression.
RBM10 (RNA Binding Motif Protein 10) is a nuclear RNA binding protein that plays critical roles in alternative splicing, gene expression regulation, and neuronal cell survival. Originally identified as a tumor suppressor in lung adenocarcinoma, RBM10 has emerged as an important player in neurodevelopment and neurodegenerative disease processes. [@inoue2021] The protein is part of the RBM family, which includes RBM5, RBM6, and other RNA-binding proteins that regulate post-transcriptional gene expression.
RBM10 is expressed predominantly in the nucleus of neurons and other cell types, where it participates in the regulation of alternative splicing events that are critical for neuronal function. Dysregulation of RBM10 function has been implicated in several neurological conditions, including neurodevelopmental disorders and potentially neurodegenerative diseases such as Alzheimer's and Parkinson's disease. [@zhang2020]
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RBM10 possesses a well-defined domain architecture that enables its RNA binding and protein-protein interaction functions. The protein contains multiple RNA recognition motif (RRM) domains, which are responsible for binding to specific RNA sequences and regulating splicing events. [@inoue2021]
The RRM domains of RBM10 are highly conserved and share structural features with other members of the RRM family. Each RRM domain consists of approximately 90 amino acids forming a four-stranded β-sheet flanked by two α-helices, creating a conserved RNA-binding fold. These domains enable RBM10 to recognize specific sequence motifs in target pre-mRNAs, particularly in intronic splicing regulatory regions.
Beyond its RNA-binding domains, RBM10 contains regions that facilitate protein-protein interactions with other splicing factors. These include interactions with components of the spliceosome machinery and other RNA-binding proteins such as RBM5, with which RBM10 shares significant homology and often collaborates in regulating shared target genes. [@sun2017]
RBM10's primary function is the regulation of alternative splicing, a critical process that increases proteomic diversity by generating multiple mRNA isoforms from a single gene. Through its RNA recognition motifs, RBM10 binds to specific sequences in pre-mRNA and modulates the inclusion or exclusion of specific exons. [@sutherland2017]
Genome-wide splicing array studies have identified numerous RBM10 target genes, including [SMN2](/genes/smn2), which encodes the Survival of Motor Neuron protein critical for spinal muscular atrophy. This connection highlights RBM10's importance in neurological function. [@sutherland2017]
Key splicing targets of RBM10 include:
RBM10 maintains tight control of its own expression through autoregulation of alternative splicing events within its own pre-mRNA. Additionally, RBM10 and its close relative RBM5 exhibit cross-regulation, where each protein influences the splicing patterns of the other. This intricate regulatory network ensures proper protein homeostasis. [@sun2017]
In non-neuronal cells, RBM10 functions as a tumor suppressor by regulating genes involved in cell cycle progression and apoptosis. Loss of RBM10 function leads to increased cell proliferation and reduced apoptosis, contributing to tumor development in lung adenocarcinoma and other cancers. [@martinez2015] [@zhao2021]
While direct evidence linking RBM10 to Alzheimer's disease remains limited, the protein's broader role in RNA processing and splicing regulation positions it as a potential contributor to neurodegenerative processes. Alternative splicing dysregulation is a well-documented feature of Alzheimer's disease, affecting genes involved in amyloid processing, tau phosphorylation, and synaptic function. [@chen2019] [@herbert2021]
The RNA binding proteins network is significantly disrupted in Alzheimer's disease, with altered expression and splicing patterns observed for multiple RBM family members. Given RBM10's role in regulating splicing events that affect neuronal survival and synaptic plasticity, it is plausible that RBM10 dysfunction could contribute to AD pathogenesis through:
Similar to Alzheimer's disease, Parkinson's disease involves widespread alterations in RNA processing and splicing. RBM10 and related RNA-binding proteins may play roles in regulating genes critical for dopaminergic neuron survival, mitochondrial function, and α-synuclein processing. [@song2019]
RBM10 mutations have been directly implicated in neurodevelopmental disorders. Notably, variants in RBM10 have been associated with TARP syndrome (Talipes equinovarus, Atrial Septal Defect, Robin Sequence, and Persistence of Left Superior Vena Cava), which includes neurological manifestations. [@owczarek2022]
De novo mutations in RBM10 have also been identified in cases of intellectual disability and autism spectrum disorder, highlighting its critical role in brain development. [@tucker2016] [@depienne2017]
Recent studies have identified RBM10 as an X-linked genetic factor that influences autoimmunity and remyelination capacity. This finding is particularly relevant for neurodegenerative conditions involving demyelination, such as multiple sclerosis. [@borziak2022]
The RNA binding properties of RBM10 make it an attractive target for therapeutic modulation. Small molecules that can modulate RBM10's splicing activity could potentially restore proper splicing patterns in neurodegenerative disease contexts. Several approaches are being explored:
Changes in RBM10 expression or splicing patterns may serve as biomarkers for neurodegenerative disease progression or treatment response. Further research is needed to establish validated clinical biomarkers based on RBM10. [@balakrishnan2017]