Research Perspective on Biological Science Vol. 12

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse group of RNA-binding proteins involved in the regulation of gene expression at multiple levels. This chapter reviews their basic biology, structural domains, cellular distribution and functional roles, with emphasis on the central nervous system (CNS). These proteins interact with pre-mRNA and mature RNA molecules and contribute to RNA splicing, stability, transport, localisation, translation, and degradation. Their distribution between the nucleus and cytoplasm supports their roles in nucleocytoplasmic transport and post-transcriptional gene regulation. The structural diversity of hnRNPs, including RNA-recognition motifs, KH domains, RGG-rich regions, and nuclear localisation or export signals, enables interactions with different RNA targets and regulatory partners. This chapter reviews the basic biology, structural organisation, cellular localisation, and functional roles of hnRNP proteins, with particular attention to their involvement in the central nervous system. In neuronal and glial cells, hnRNPs contribute to mRNA trafficking, axonal and dendritic regulation, synaptic organisation, cytoskeletal control, and activity-dependent RNA metabolism. The chapter also discusses the participation of hnRNPs in chromatin organisation, epigenetic regulation, telomere-related processes, and genome stability. Dysregulation of hnRNP expression, localisation, or RNA-binding activity is associated with several neurological and neurodevelopmental conditions, including multiple sclerosis, fragile X-associated tremor/ataxia syndrome, congenital myasthenic syndrome, Alzheimer’s disease, spinal muscular atrophy, and related disorders. Therapeutic approaches involving RNA-based strategies, antisense oligonucleotides, small molecules, proteostasis modulation, and genome-editing methods are discussed as emerging areas of interest. However, selective targeting of hnRNPs remains challenging because of their multifunctional roles, overlapping activities, and broad involvement in essential cellular processes. A clearer understanding of hnRNP-mediated mechanisms may support future biomarker discovery and the development of more precise therapeutic strategies for CNS and other human diseases.