Identification of Tissue Specific Splice Variants and Isoforms of RNA Exosome in Mice Público

Abstract

The RNA exosome is a 10-subunit complex required for the processing, turnover, and degradation of many classes of RNA. This complex is highly conserved, essential for survival, and ubiquitously expressed in all tissues and cell types. Nine of the ten subunits are structural. EXOSC1, EXOSC2, and EXOSC3 make up the cap of the complex. EXOSC4, EXOSC5, EXOSC6, EXOSC7, EXOSC8, and EXOSC9 make up the core. The cap and the core form a hollow barrel for which RNA is threaded through to reach the catalytic base subunit, DIS3, a 3’-5’ endo/exoribonuclease. Although the RNA exosome is essential and expressed in all cell types, missense mutations in the genes encoding several structural subunits have been linked to rare diseases that primarily cause neurological pathology, many of them severe childhood neuronopathies. One explanation for why the RNA exosome subunit gene mutations give rise to brain-specific diseases is that the structural subunit genes could be differentially spliced in specific tissues. Little is understood about the tissue-specific expression of the RNA exosome subunit splice variants, despite the existence of known variants. Here, we examine the steady-state levels of RNA exosome subunit mRNA and protein across various tissues. We find that the RNA exosome subunit isoforms have differences that may influence the ability of the RNA exosome to interact with cofactors and/or substrates. 

Table of Contents

Introduction ................................................................................................................................. 1

Materials and Methods ............................................................................................................. 3

Results .......................................................................................................................................... 7

Discussion ................................................................................................................................. 12 References................................................................................................................................. 18

Figures ........................................................................................................................................ 20

Supplemental Figures............................................................................................................. 28 

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, General
Palabra Clave	EXOSC1 EXOSC9 Isoforms Tissues RNA exosome EXOSC3 Splice variants
Committee Chair / Thesis Advisor	Anita H. Corbett, Emory University
Committee Members	Roger Deal, Emory University Homa Ghalei, Emory University

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