The Emerging Role of the RNA-Binding Protein SFPQ in Neuronal Function and Neurodegeneration

Abstract

RNA-binding proteins (RBPs) are a class of proteins known for their diverse roles in RNA biogenesis, from regulating transcriptional processes in the nucleus to facilitating translation in the cytoplasm. With higher demand for RNA metabolism in the nervous system, RBP misregulation has been linked to a wide range of neurological and neurodegenerative diseases. One of the emerging RBPs implicated in neuronal function and neurodegeneration is splicing factor proline- and glutamine-rich (SFPQ). SFPQ is a ubiquitous and abundant RBP that plays multiple regulatory roles in the nucleus such as paraspeckle formation, DNA damage repair, and various transcriptional regulation processes. An increasing number of studies have demonstrated the nuclear and also cytoplasmic roles of SFPQ in neurons, particularly in post-transcriptional regulation and RNA granule formation. Not surprisingly, the misregulation of SFPQ has been linked to pathological features shown by other neurodegenerative disease-associated RBPs such as aberrant RNA splicing, cytoplasmic mislocalization, and aggregation. In this review, we discuss recent findings on the roles of SFPQ with a particular focus on those in neuronal development and homeostasis as well as its implications in neurodegenerative diseases.

Splicing factor proline and glutamine rich intron retention, reduced expression and aggregate formation are pathological features of amyotrophic lateral sclerosis

“…SFPQ, also known as polypyrimidine tract‐binding protein‐associated splicing factor, PSF, is a predominantly nuclear protein with a range of functions required for cell development and survival, including DNA repair, transcriptional regulation, post‐transcriptional RNA processing, paraspeckle formation and axonal transport [8, 9]. Dysregulation of SFPQ has been linked to multiple neurodegenerative diseases [10]. SFPQ nuclear depletion and altered expression have been reported in animal models and small case–control studies of Alzheimer's disease (AD) and frontotemporal dementia (FTD) [11–13].…”

Proteomics-based determination of double stranded RNA interactome reveals known and new factors involved in Sindbis virus infection

“…One of such proteins we identified was SFPQ, an ubiquitous and abundant protein implicated in many aspects of nucleic acid biology in the nucleus, ranging from genome stability to transcription, as well as pre-mRNA splicing and 3’end RNA processing or nuclear retention (27). Although SFPQ is strongly localized in the nucleus under normal circumstances, several reports have shown that it may also have important non-nuclear functions such as mRNA post-transcriptional regulation and RNA granule formation especially in neurons (38).…”

Identifying Novel Actionable Targets in Colon Cancer

“…Moreover, it binds to DNA by forming an SFPQ-NONO heterodimer, which participates in homologous DNA pairing and in DNA non-homologous end joining (NHEJ) required for double-strand break repair. Finally, SFPQ is involved in transcriptional regulation as a transcriptional activator [150,151]. Since monotherapies blocking downstream components of the MAPK signaling pathway have been unsatisfactory in CRC because of pathway reactivation, Klotz-Noack and colleagues hypothesized that interference with nuclear proteins activated by MAPK might open a window of opportunity for precisely eliminating MAPK-driven CRCs.…”