Table 1.

Basic molecular functions and roles in neuronal homeostasis and disease.

Protein	Binding Motif(s)	Main Functions	Human-Associated Pathology	Rodent Knockouts
Pumilio	UGUANAUA	Translation repressor Induce SG assembly RNP granule transport	Temporal Lobe Epilepsy (TLE)	Reduced number of neural stem cells Enhanced dendritic outgrowth and arborization SCA1-like neurodegeneration Progressive motor dysfunction Impaired learning and memory
Staufen	RNA stem–loops	RNP granule transport Polarized mRNA transport Inhibit SG assembly Translation enhancement Staufen mediated decay (SMD)	-	Reduced number of neural stem cells Reduced dendritic tree arborization Fewer synapses Deficits in locomotor activity
Insulin-like Growth Factor 2 mRNA-Binding Protein (IGF2BP)	CAUH (H = A, U, or C) or CA-rich motifs	RNP transport Translation inhibition	-	Perinatal death Smaller animal size Compromised central and peripheral synaptogenesis PSC and NSC depletion and accelerated differentiation Axonal growth deficits after peripheral nerve injury
FragileX Mental Retardation Protein (FMRP)	TGGA	Transcriptional activation Alternative splicing Inhibit RNA A-I editing Translation inhibition RNP transport miRISC recruitment on target DNA damage response	Fragile-X Syndrome (FXS) Fragile-X-Associated Tremor/Ataxia Syndrome (FXTAS)	More and shorter dendritic spines and delayed maturation Reduced mobility of growth cones Deficits in learning and memory Hyperactivity
Src-Associated substrate in Mitosis of 68 kDa (Sam68)	UAAA or UUAA	Intracellular signaling adaptor Promotes translation Alternative splicing RNP granule transport Proapoptotic roles after injury	Fragile-X-Associated Tremor /Ataxia Syndrome (FXTAS) Spinal Muscular Atrophy (SMA)	Reduced NPC proliferation Fewer dendritic spines Motor coordination deficits
Cytoplasmic Polyadenylation Element Binding protein (CPEB)	UUUAU or UUUUAAU	Cytoplasmic polyadenylation Alternative Polyadenylation RNP granule transport Local translation Promote SG assembly	-	Impaired mitochondrial function Reduced dendritic mRNA transport Reduced theta burst-induced LTP Inability to extinguish memories Motor coordination deficits Motor learning delay
Neuro-Oncological Ventral Antigen (NOVA)	YCAY (Y is C or U)	Alternative splicing Alternative polyadenylation Inhibit nonsense mediated decay RNP granule transport	Paraneoplastic Opsoclonus Myoclonus Ataxia (POMA)	Nova1 KO: Death within 3 weeks of birth Axonal outgrowth defects Profound motor failure Nova2 KO: Death within 2 weeks of birth Aberrant migration of cortical and Purkinje neurons Axonal outgrowth defects No LTP following external stimulation Double KO: death soon after birth due to lack of lung motor innervation
Embryonic Lethal/Abnormal Vision-Like (ELAVL)	U-rich (with G or A intermittently)	Transcription rate Alternative splicing Alternative polyadenylation Compete with miRNA binding to mRNAs mRNA stability Translation enhancement RNP transport	Paraneoplastic Encephalomyelopathy/Paraneoplastic Sensory Neuropathy (PEM/PSN) Schizophrenia Parkinson’s disease (PD)	Neuron targeted HuR KO: motor neuron disease (poor balance, decreased movement and strength) HuC KO: Purkinje cell impaired functionality and morphology; Cerebral Ataxia; Epileptic seizures; Impaired spatial learning HuD KO: Impaired spatial learning; Lower levels of anxiety and activity; Predisposition towards auditory-induced seizures; Fewer differentiated neurons; Reduced axodendritic complexity; Cortical and motor deficits HuC/D doubleKO: perinatal death
Survival Motor Neuron (SMN)	not an RBP	snRNP assembly Alternative splicing RNP granule transport Axonal protein synthesis Induce SG assembly	Spinal Muscular Atrophy (SMA)	Embryos die prenatally Reduced association of RNPs with microtubules and actin filaments Shorter neurites, fewer branches and poor terminal arborization Enhanced neuronal death Smaller RNP granules
TAR DNA-binding Protein 43 (TDP43)	UG repeats	Alternative splicing mRNA stability RNP granule transport Induce SG assembly miRNA biogenesis Translation regulation Nuclear pore transport	Familial Amyotrophic Lateral Sclerosis (fALS) Frontotemporal dementia (FTD) Alzheimer’s Disease (AD) Dementia with Lewy bodies (DLB) Huntington’s Disease (HD)	Degeneration of large motor axons Skeletal muscle grouped atrophy Denervation of the neuromuscular junction
Fused in Sarcoma (FUS)	GUGGU	Alternative splicing Alternative polyadenylation Nucleocytoplasmic shuttling miRNA biogenesis RNP granule transport DNA damage response	Familial Amyotrophic Lateral Sclerosis (fALS) Frontotemporal dementia (FTD)	Perinatal lethality Enhanced neuronal cell death
TATA-box binding protein Associated Factor 15 (TAF15)	GGUAAGU	Alternative splicing RNA stability RNP granule transport	Familial Amyotrophic Lateral Sclerosis (fALS)	-
T-cell-restricted Intracellular Antigen 1 (TIA1) & TIA1-Related (TIAR)	T-rich motifs (DNA) U-rich motifs (RNA)	Alternative splicing Translation inhibition SG nucleation/assembly Inhibit nonsense mediated decay DNA damage response	Familial Amyotrophic Lateral Sclerosis (fALS) Tauopathies	TIAR: embryonic lethality TIA1: high rate of perinatal death, widespread inflammation TIA1/TIAR doubleKO: embryonic lethality