Biology subjects

Buchanan, C. N.

Publications and source records attributed to Buchanan, C. N..

3 recordsLinked to original sources

bioRxiv2026

Multiple mTOR RNA localization signals regulate subcellular protein synthesis and axonal growth

Subcellular localization of mTOR is thought to be key for regulating cell size and growth, but the relative contributions of mRNA versus protein localization are unclear. We used reporter mRNA localization assays to identify two distinct mTOR Localizing Sequences (MLS) in its 5UTR, in addition to the localization activity already reported for the 3UTR. Gene-edited mice with deletion of both 5UTR MLS are mTOR hypomorphs with reduced body weight and brain size. In contrast, a mouse line lacking the second 5UTR MLS and the 3UTR retains near normal overall mTOR expression levels with specific subcellular perturbation of mTOR localization to neuronal axons. This subcellular mTOR deficit affects axonal local protein synthesis and neuronal growth. Thus, mTOR transcripts are localized by multiple UTR sequences, and subcellular localization of mTOR mRNA regulates local protein synthesis and neuronal growth.

neuroscience↗

bioRxiv2025

Acetylation of Axonal G3BP1 through ELP3 Accelerates Axon Regeneration

Nerve injury triggers localized translation of axonal mRNAs to respond to injury and nerve regeneration. The core stress granule protein G3BP1 sequesters axonal mRNAs in granules before and after axotomy. G3BP1 granule disassembly can be regulated by post-translational modifications, including phosphorylation of S149 phosphorylation and acetylation of human K376 (mouse K374). Axonal G3BP1 undergoes phosphorylation after axotomy, but acetylation of G3BP1 in axons was unknown. Here we show that rodent G3BP1 undergoes K374 acetylation after axotomy is ELP3-dependent, which enhances axonal protein synthesis, accelerates nerve regeneration, and supports functional recovery. ELP3-depleted neurons exhibit reduced axon growth and increased axonal G3BP1 granules. The proximal axons degenerate rapidly despite maintaining soma connectivity, an effect prevented by expression of acetylmimetic G3BP1.Together, these findings identify G3BP1 acetylation via ELP3 as a critical regulator of both axonal regeneration and neuronal resilience, revealing a post-translational mechanism that links stress granule regulation to neuronal repair and protection.

neuroscience↗

bioRxiv2025

An axon-intrinsic loop restricts nerve regeneration through axonal protein synthesis

Injured axons synthesize the RNA Binding Protein KHSRP that promotes mRNA decay and slows nerve regeneration. Axotomy-induced increase in axoplasmic Ca2+ activates axonal Khsrp translation, and while Ca2+ returns to pre-injury levels within 16 hours post-axotomy, axonal KHSRP remains elevated. Alternating translation of Reg3a and Khsrp sustains axonal KHSRP levels in regenerating axons. Nerve injury activates Reg3a expression, resulting in increased REG3A synthesis and secretion from axons. REG3A stimulates ER Ca2+ release to activate PERK, increase eIF2 phosphorylation, and increase Khsrp translation. Axoplasmic Ca2+ slowly oscillates in growth cones and Reg3A depletion attenuates growth cone Ca2+ oscillations, decreases KHSRP synthesis, reduces the axons retractive events, and accelerates peripheral nerve regeneration. Thus, REG3A to KHSRP signaling provides an axon-intrinsic loop that decelerates axon growth through localized mRNA translation.

neuroscience↗