2026-09-20T08:03:57Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/1113142022-01-13T07:53:55Zcom_1721.1_7582com_1721.1_7581col_1721.1_131023
Christopher B. Burge.
Srinath, Chetan
Massachusetts Institute of Technology. Department of Biology.
Massachusetts Institute of Technology. Department of Biology
2017-09-15T15:28:43Z
2017-09-15T15:28:43Z
2017
2017
http://hdl.handle.net/1721.1/111314
1003289754
Thesis: S.M., Massachusetts Institute of Technology, Department of Biology, 2017.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 45-50).
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.
by Chetan Srinath.
S.M.
50 pages
eng
Massachusetts Institute of Technology
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.
http://dspace.mit.edu/handle/1721.1/7582
Biology.
mRNA stability in soma and neurites of cultured neuronal cells
Thesis
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<Abstract>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.</Abstract>
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