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Chemoproteomic Approaches for Assaying Translation

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서명/저자사항Chemoproteomic Approaches for Assaying Translation.
개인저자Khitun, Alexandra.
단체저자명Yale University. Chemistry.
발행사항[S.l.]: Yale University., 2019.
발행사항Ann Arbor: ProQuest Dissertations & Theses, 2019.
형태사항161 p.
기본자료 저록Dissertations Abstracts International 81-03B.
Dissertation Abstract International
ISBN9781085777155
학위논문주기Thesis (Ph.D.)--Yale University, 2019.
일반주기 Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Slavoff, Sarah A.
이용제한사항This item must not be sold to any third party vendors.
요약Small open reading frames (<100 codons) are a repository of functional protein code which have been heretofore ignored due to artificial cut-offs imposed during genome annotation of virtually all organisms. In addition to encoding biologically active small proteins, small open reading frames also act as important translational regulatory elements which have shed light on the plasticity of some translation initiation steps.In eukaryotes, translation is a highly coordinated process that commences with the recognition of the 5' N7-methylguanosine cap of mRNA by protein eIF4E and proceeds through recruitment of the ribosome which scans the transcript for an AUG start codon. However, in some contexts, a subset of transcripts may evade this mechanism. During stress conditions when global translation is arrested transcripts with specialized post-transcriptional modifications or sequence motifs maintain capacity for protein synthesis. Similarly, previously thought to be non-coding regions of transcripts can produce protein through initiation at non-AUG start codons.This work describes a set of proteomic experiments that aim to detect and quantify regulated translation events. Chapter 1 introduces the subject of stress-regulated translation in detail, focusing on translation from small open reading frames in both prokaryotes and eukaryotes. Chapter 2 describes the discovery of bacterial stress-regulated small proteins using a semi-quantitative proteomic approach. Chapter 3 gives an example of a small protein encoded on a long non-coding RNA that mediates mucosal immunity in mice, and is conserved in humans. Chapter 4 outlines the discovery of a dual-coding transcript that co-encodes a ribosomal protein and a protein of unknown function. Chapter 5 introduces a chemical labeling strategy that uniquely facilitates detection of non-annotated proteoforms in human cells. Chapter 6 focuses specifically on stress-regulated translation in eukaryotes, and the detection of a stress-induced eIF4E regulon, Sec28, in yeast.
일반주제명Chemistry.
Biology.
언어영어
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