Photochemical Sciences Ph.D. Dissertations

Analysis of RNA 3D Folding: PART I. How to Fold a Complex RNA with Few Guanines: The Case of the Mammalian Mitochondrial Ribosomal RNA. PART II. Resolving Ambiguities in RNA Multi-Helix Junction (MHJ) Loops and Automatic Extraction of Them

Date of Award

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Photochemical Sciences

First Advisor

Neocles Leontis (Advisor)

Second Advisor

Arthur Samel (Other)

Third Advisor

R. Marshall Wilson (Committee Member)

Fourth Advisor

Craig Zirbel (Committee Member)

Abstract

This dissertation comprises three distinct parts; however, all parts are linked by their complementary approaches to investigate the nature of RNA structure.

The first part of this dissertation is a study on the evolution of the Mammalian mitochondrial (mmt) ribosomes in a highly oxidative environment. Mmt ribosomes evolved from bacterial ribosomes by reduction of ribosomal RNAs, increase of ribosomal protein content, and loss of guanine nucleotides; they translate only 13 polypeptides of the electron transport chain (ETC); they are exposed to reactive oxygen species (ROS) generated by the ETC, and appear to turn over every 4-5 hours, at a rate ~24 times faster than for cytosolic ribosomes.1 Therefore, they are subject to strong selection pressure favoring structural changes that reduce or limit oxidative damage. In this part, we address two important questions. First, how can a complex RNA structure fold with fewer Gs? Second, why there is such a reduction in the G content in the mmt structure and why are Gs avoided?

In the second part of this dissertation the ambiguities of RNA Multi-helix Junction (MHJ) loops are discussed. MHJ loops are key organizing elements of RNA architectures; they provide branch points to increase RNA structural complexity and functional potential. MHJ loops form when more than two RNA helices come together.2 Almost all structured RNAs contain MHJ loops, which can vary in size from three (3WJ) to ten (10WJ) or more converging helices. Extraction and classification of RNA MHJ loops aids better understanding of RNA structure and its function in the cell. Previous workers have published methods for finding and extracting MHJ loops in RNA,3-5 however there remain some important outstanding issues to resolve in order to achieve the level of precision and comprehensiveness needed for correct extraction of the MHJs. These are: 1) Distinguishing embedded Watson-Crick (WC) base pairs that are integral components of MHJ from flanking WC base pairs. Correctly determining the flanking WC base pairs that define the locations of all RNA loop motifs is the first step to precisely extract RNA MHJ loops; 2) addressing the ambiguity of MHJ size created by the presence of pseudoknot base pairs within some MHJ.

The third part of the thesis focuses on the detection and automatic extraction of the Multi-helix Junction (MHJ) loops. We write a pseudo code to detect and extract RNA MHJ loops with resolving MHJ loops formed by embedded WC and pseudoknot base pairs.

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