Devon Chenette

Highlights • Candidate genes are screened for optic nerve regeneration effects by AAV-shRNA • Regeneration-limiting genes are confirmed by AAV CRISPR-Cas9 gene editing • Validated regeneration-limiting genes do not show axotomy-regulated expression • IL-22 loss activates both Stat3 and DLK, with upregulation of multiple pathways Summary Adult mammalian central nervous system (CNS) trauma interrupts neural networks and, because axonal regeneration is minimal, neurological deficits persist.

Abstract Regulated messenger RNA (mRNA) decay is an essential mechanism that governs proper control of gene expression. In fact, many of the most physiologically potent proteins are encoded by short‐lived mRNAs, many of which contain AU‐rich elements (AREs) in their 3′‐untranslated region (3′‐UTR). AREs target mRNAs for post‐transcriptional regulation, generally rapid decay, but also stabilization and translation inhibition.

Significance A major unresolved issue for premenopausal women undergoing chemotherapy is infertility due to the loss of nonrenewable ovarian primordial follicles. We show that pharmacologic down-regulation of the mammalian/mechanistic target of rapamycin (mTOR) pathway during chemotherapy in a mouse model prevents activation of primordial follicles, preserves ovarian function, and maintains normal fertility using clinically available inhibitors of mTOR complex (C)1 and mTORC1/2.