Models of dynamic RNA regulation in mammalian cells
Thesis (Ph. D.)--Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2013.
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | eng |
| Published: |
Massachusetts Institute of Technology
2014
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/1721.1/84894 |
| _version_ | 1811096904615854080 |
|---|---|
| author | Rabani, Michal |
| author2 | Aviv Regev. |
| author_facet | Aviv Regev. Rabani, Michal |
| author_sort | Rabani, Michal |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2013. |
| first_indexed | 2024-09-23T16:51:14Z |
| format | Thesis |
| id | mit-1721.1/84894 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T16:51:14Z |
| publishDate | 2014 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/848942019-04-11T10:57:34Z Models of dynamic RNA regulation in mammalian cells Models of dynamic Ribonucleic Acid regulation in mammalian cells Rabani, Michal Aviv Regev. Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science. Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science. Electrical Engineering and Computer Science. Thesis (Ph. D.)--Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2013. Cataloged from PDF version of thesis. Includes bibliographical references (pages 135-142). Complex molecular circuits, consisting of multiple intertwined feedback loops and non-linear interactions, are a hallmark of every living cell, and a model of a dynamic complex network. Here, I systematically study the dynamic changes in the cellular circuits that control RNA levels in mammalian cells, focusing on the model response of immune dendritic cells to pathogens, through an integration of comprehensive computational models and innovative empirical approaches. I establish a computational framework to follow the dynamics of processes for RNA birth (production, by transcription), maturation (processing), and death (degradation), and their integration in the dynamic RNA life cycle. I study the kinetics of a gene's RNA population with a model of its production and degradation, and generalize the system as an ensemble of genes. I further model genes as composite particles and study the regulation and kinetics of altering their internal structure. To allow robust statistical inference from these models, I develop innovative laboratory assays and collect extensive experimental data on the system. I directly measure RNA production rates by coupling short RNA metabolic labeling with advanced RNA quantification. I leverage recent improvements in RNA quantification by next-generation sequencing technology, to significantly increase the resolution of metabolic labeling in both time and gene-structure. Finally, I collect perturbation data, by monitoring RNA levels when specific elements of the network are disabled. In this way, I formulated several general principles of RNA regulation and its temporal evolution in mammalian cells. I find that temporal changes in production provide a dominant input in computing RNA levels by the cell over time. Yet, dynamic degradation changes contribute to shaping expression peaks, and dynamic processing changes allow a fast accumulation of mature transcripts. Static degradation and processing rates vary between genes and between individual splicing junctions, consistently with their function and expression dynamics. This study is broadly applicable to many normal as well as diseases misregulated cellular networks, and is also relevant for a more general analysis of complex systems dynamics. by Michal Rabani. Ph.D. 2014-02-10T16:59:38Z 2014-02-10T16:59:38Z 2013 Thesis http://hdl.handle.net/1721.1/84894 868825521 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 142 pages application/pdf Massachusetts Institute of Technology |
| spellingShingle | Electrical Engineering and Computer Science. Rabani, Michal Models of dynamic RNA regulation in mammalian cells |
| title | Models of dynamic RNA regulation in mammalian cells |
| title_full | Models of dynamic RNA regulation in mammalian cells |
| title_fullStr | Models of dynamic RNA regulation in mammalian cells |
| title_full_unstemmed | Models of dynamic RNA regulation in mammalian cells |
| title_short | Models of dynamic RNA regulation in mammalian cells |
| title_sort | models of dynamic rna regulation in mammalian cells |
| topic | Electrical Engineering and Computer Science. |
| url | http://hdl.handle.net/1721.1/84894 |
| work_keys_str_mv | AT rabanimichal modelsofdynamicrnaregulationinmammaliancells AT rabanimichal modelsofdynamicribonucleicacidregulationinmammaliancells |