Work

MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration

Year: 2013

Type: preprint

Abstract: Regulated gene expression determines the intrinsic ability of neurons to extend axons, and loss of such ability is the major reason for the failed axon regeneration in the mature mammalian CNS. MicroRNAs and histone modifications are key epigenetic regulators of gene expression, but their roles in mammalian axon regeneration are not well explored. Here we report microRNA-138 (miR-138) as a novel suppressor of axon regeneration and show that SIRT1, the NAD-dependent histone deacetylase, is the functional target of miR-138. Importantly, we provide the first evidence that miR-138 and SIRT1 regulate mammalian axon regeneration in vivo. Moreover, we found that SIRT1 also acts as a transcriptional repressor to suppress the expression of miR-138 in adult sensory neurons in response to peripheral nerve injury. Therefore, miR-138 and SIRT1 form a mutual negative feedback regulatory loop, which provides a novel mechanism for controlling intrinsic axon regeneration ability.

Source: Genes & Development

DOI: 10.1101/gad.209619.112

Authors: Chang-Mei Liu, Rui-Ying Wang, Saijilafu, Zhong-Xian Jiao, Bo-Yin Zhang, Feng-Quan Zhou

Institutions: Johns Hopkins University, Johns Hopkins Medicine, Guilin Medical University

Language: English

Topic: Nerve injury and regeneration

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Craig H. Neilsen Foundation, National Institutes of Health, National Institute of Neurological Disorders and Stroke