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Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp01h128nh40v
Title: THE ROLE OF REGULATED RNA DECAY BY RNASE L IN HOMEOSTASIS AND INNATE IMMUNITY
Authors: Rath, Sneha Prakash
Advisors: Korennykh, Alexei V.
Contributors: Molecular Biology Department
Keywords: dsRNA stress
Innate immunity
Interferon response
OAS/RNase L
Translation control
Tumor suppressor
Subjects: Molecular biology
Issue Date: 2018
Publisher: Princeton, NJ : Princeton University
Abstract: Mammalian cells are equipped with mechanisms to fight infections directly and rapidly before adaptive immunity can be invoked. Activation of these immediate mechanisms is called the innate immune response and universally involves induction of interferons and inflammatory cytokines. When innate immunity is triggered by immunogenic double-stranded RNA (dsRNA), the cells additionally start cleaving their own RNAs due to activation of an unusual receptor kinase-endoribonuclease, RNase L. We combine X-ray crystallography, biochemistry, cell biology and RNA-seq to decipher the function of RNase L-induced RNA decay in dsRNA response. Our work identified the first direct cellular RNA targets of human RNase L. From this work RNase L emerges as a sharp, yet tunable, instrument of the innate immune system. Under homeostasis, this instrument controls the levels of select mRNAs to inhibit proliferation and metastasis, resembling the action of tumor-suppressing microRNAs such as miR-200. On the other hand, under acute dsRNA stress, RNase L rapidly blocks global translation and creates a privileged landscape for interferon synthesis. This work illuminates how RNase L is repurposed for distinct functions from homeostasis to innate immune response based on dsRNA load.
URI: http://arks.princeton.edu/ark:/88435/dsp01h128nh40v
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: catalog.princeton.edu
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Molecular Biology

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