Upf1 regulates neurite outgrowth and branching by transcriptional and post-transcriptional modulation of Arc

Abstract

A large number of neuronal proteins must show correct spatiotemporal localization in order to carry out their critical functions. The mRNA transcript for the somatodendritic protein activity-regulated cytoskeleton-associated protein (Arc; also known as Arg3.1) contains two conserved introns in the 3′ untranslated region (UTR), and was proposed to be a natural target for nonsensemediated mRNA decay (NMD). However, a well-known NMD component Upf1 has differential roles in transcriptional and translational regulation of Arc gene expression. Specifically, Upf1 suppresses Arc transcription by enhancing destabilization of mRNAs encoding various transcription factors, including Mef2a. Upf1 also binds to the Arc 3′UTR, resulting in suppression of translation. Surprisingly, the Arc transcript escapes from Upf1-mediated NMD by binding to Ago2 (also known as miRISC), which blocks NMD and further suppresses Arc mRNA translation. Upf1 knockdown triggered sustained Arc expression, which contributes to Cofilin (also known as Cfl1) hyperphosphorylation and abnormal neuronal outgrowth and branching. Collectively, these data reveal that multiple levels of Upf1-mediated inhibition of Arc gene expression may allow neurons to more effectively respond to changes in neuronal activity.

Phosphorylated Upstream Frameshift 1–dependent Nonsense-mediated μ-Opioid Receptor mRNA Decay in the Spinal Cord Contributes to the Development of Neuropathic Allodynia–like Behavior in Rats

“…Spinal nerve ligation significantly increased the expression of phosphorylated UPF1, but not that of total UPF1, in the ipsilateral dorsal horn in rats on Days 3, 7, 14, and 21 after the operation with a time course that was consistent with that observed in spinal nerve ligation-induced allodynia-like behaviors in rats (fig. 1B 3,7,14,21] in the nerve ligation ipsilateral group, P = 0.025, P < 0.001, P < 0.001, and P = 0.004; [Day -1] in the nerve ligation ipsilateral group vs. [ Day 3,7,14,21] in the nerve ligation ipsilateral group, all P < 0.001). These results indicated that spinal phosphorylated UPF1 Days -1 and 7 after spinal nerve ligation operation in male or female rats.…”

“…2 Notably, the UPF1-regulated translation of mRNAs is critical for synaptic plasticity because UPF1 knockdown triggers abnormal neuronal outgrowth and branching. 3 Moreover, the content of UPF1 impacts the homeostatic excitation/inhibition balance in neurons. 4 Studies have demonstrated that activity-dependent synaptic plasticity in the spinal (central sensitization) plays a key role in nociception mechanism.…”

HNRNP A1 Promotes Lung Cancer Cell Proliferation by Modulating VRK1 Translation

“…RNA isolation and cDNA synthesis were performed as we previously described [ 39 ]. Cells were lysed with TRI-Solution (Bio Science Technology, Cat.# TS100-001) and the total RNA was extracted.…”

A Fluorescent Vector of Carbon Dot to Deliver Rab13 and Rab14 Plasmids for Promoting Neurite Outgrowth

“…Many studies have demonstrated that neurite extension can be mediated by many growth factors and small molecules, including the nerve growth factor, Rac1, RhoA, SORLA, and phosphoglycerate kinase 1. ,,,− Furthermore, more than 60 types of Rab proteins have been found in mammals; these proteins belong to the Ras GTPase superfamily and are located in distinct subcellular compartments to regulate the budding, tethering, fusion, and transport of vesicles in vesicle-mediated transport . Several Rab proteins have been demonstrated to play crucial roles in mediating the axonal polarization and elongation of neuronal cells.…”

“…Moreover, traumatic brain injury is a temporary or permanent disruption of brain function by external physical force and can cause disability, mental disorders (such as dementia), or death among patients. − Because of the limited intrinsic repair and regeneration ability of CNS after injury and disorder, promoting neuron differentiation and repair is crucial for the treatment of CNS-injury-related diseases. , Consequently, many studies have attempted to achieve synaptic polarization and plasticity, neurite elongation, and neuron differentiation . These studies have focused on growth factors, drugs, and small molecules for stimulating signaling pathways to enhance neurite growth; external physical and mechanical cues for guiding neurite extension; and artificial scaffolds and biomaterials for supporting neurite outgrowth. − …”