mRNA stability in soma and neurites of cultured neuronal cells

Neurons rely on mRNA localization and local protein synthesis in neurites to regulate synaptic plasticity, axonogenesis and neural signaling. The local regulation of mRNA stability in neurites is poorly understood. To determine mRNA decay rates, we analyzed the subcellular transcriptomes of neural projections and soma of mouse neuronal cells following inhibition of transcription with actinomycin-D. Less stable transcripts were enriched for GU-rich elements in their 3' UTRs. Around 12% of alternative splicing isoform pairs differed in stability, and cassette alternative ("skipped") exons that negatively impact stability are enriched for A-rich sequences. Overall, decay rates were similar across soma and neurites. However, differences in stability between soma and neurites were observed for GC-rich alternative first exon isoforms, which were preferentially stabilized in neurites. Our results suggest that 5' UTRs may play a key role in regulating local mRNA stability in neurites.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2017

Author dc:creator

• Srinath, Chetan

Advisor dc:contributor.advisor

• Christopher B. Burge.

• Biology.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/111314

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/111314