CRISPR adaptation to RNA

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Abstract/Contents

Abstract
Cells use a variety of mechanisms to mitigate the threat of genetic invasions and to prevent the propagation of parasitic information. A family of prokaryotic adaptive immune systems associated with Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) arrays has been shown to protect cell populations from "selfish DNA" such as plasmids and viruses. CRISPR-mediated immunity begins with an "adaptation" phase in which the host acquires short sequence segments (spacers) from the genome of the infectious agent. The spacers are stored within CRISPR arrays in the host genome and serve as heritable molecular memories of the invader. This information is used by CRISPR-associated (Cas) nucleases in the subsequent "interference" phase to identify and disrupt future infections by the same invader. Most CRISPR-Cas systems can be phylogenetically classified into three major types. Type I and Type II systems acquire spacers from (and subsequently interfere with) DNA sequences, while Type III systems additionally target RNA sequences for degradation. In the absence of any known mechanisms for CRISPR adaptation to RNA, this was believed to be an auxiliary mode of attack against DNA parasites. We discovered that some Type III systems can acquire spacers directly from RNA, suggesting that these CRISPR-Cas systems could learn to fend off RNA parasites as well. This system represents, to our knowledge, the first identified cellular process in which sequence information is actively acquired from RNA and deposited (as DNA) into the genome at the behest of the host cell. Moreover, direct acquisition of RNA spacers into CRISPR arrays represents a novel and uniquely sequence-agnostic mode among the handful of known mechanisms for reverse flow of genetic information from RNA into DNA genomes, including reverse transcription machineries associated with retroviruses, telomeres, retrotransposons, mobile group II introns, and phage diversity generating elements.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2017
Issuance monographic
Language English

Creators/Contributors

Associated with Silas, Sukrit
Associated with Stanford University, Department of Chemical and Systems Biology.
Primary advisor Fire, Andrew Zachary
Thesis advisor Fire, Andrew Zachary
Thesis advisor Jarosz, Daniel
Thesis advisor Kirkegaard, Karla
Thesis advisor Meyer, Tobias
Advisor Jarosz, Daniel
Advisor Kirkegaard, Karla
Advisor Meyer, Tobias

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Sukrit Silas.
Note Submitted to the Department of Chemical and Systems Biology.
Thesis Thesis (Ph.D.)--Stanford University, 2017.
Location electronic resource

Access conditions

Copyright
© 2017 by Sukrit Silas
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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