한빛사논문
- 조회490
Jane Jung 1,4, Jiyeon Ohk 1,4, Hyeyoung Kim 1,4, Christine E. Holt 2, Hyun Jung Park 3, Hosung Jung 1,5
1Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
2Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK
3Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea
4These authors contributed equally.
5Lead contact
Corresponding authors: Hyun Jung Park, Hosung Jung
Abstract
Localized mRNA translation regulates synapse function and axon maintenance, but how compartment-specific mRNA repertoires are regulated is largely unknown. We developed an axonal transcriptome capture method that allows deep sequencing of metabolically labeled mRNAs from retinal ganglion cell axon terminals in mouse. Comparing axonal-to-somal transcriptomes and axonal translatome-to-transcriptome enables genome-wide visualization of mRNA transport and translation and unveils potential regulators tuned to each process. FMRP and TDP-43 stand out as key regulators of transport, and experiments in Fmr1 knockout mice validate FMRP's role in the axonal transportation of synapse-related mRNAs. Pulse-and-chase experiments enable genome-wide assessment of mRNA stability in axons and reveal a strong coupling between mRNA translation and decay. Measuring the absolute mRNA abundance per axon terminal shows that the adult axonal transcriptome is stably maintained by persistent transport. Our datasets provide a rich resource for unique insights into RNA-based mechanisms in maintaining presynaptic structure and function in vivo.
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2023-02-10)
- 국내(교신)+국외 연구진
- 의약학 > 분자세포의학
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