Regulation, nuclear retention, and organization of long-non-coding RNA hsr-omega into nuclear domains

Author

Sharar Naiarin Haque

Date of Award

Spring 5-2-2025

Degree Type

Dissertation/Thesis

Degree Name

Master of Science in Integrative Biology

Department

Molecular and Cellular Biology

Committee Chair/First Advisor

Anton Bryantsev

Second Advisor

Andrew Haddow

Third Advisor

Scott Nowak

Abstract

Discovered at the dawn of microscopy, the cell nucleus caught scientific attention due to its behavior during cell division and its roles in fertilization and inheritance. Apart from containing genetic information and serving as the location for DNA and RNA synthesis, transcription, and processing, it also plays a crucial role in coordinating the complex cellular architecture.

Research into the physical and functional status of the nucleus has uncovered a high degree of organization and dynamic behavior within the nucleus. The complexity of the cell nucleus is adorned by a diverse range of components such as polymers, colloids, small molecules, and macromolecules. Despite the absence of internal boundaries and membranes, the nucleus exhibits partitioning of its content into distinct domains that differ by molecular composition and functionality. The intriguing nature of the nucleus demands innovative experimental and analytical approaches involving physics, biophysics, and statistical mechanics, while also integrating knowledge from biochemistry and molecular biology. Understanding how these different parts stand together, communicate, and work together requires a multidisciplinary perspective.

In this study, we used a combination of molecular and cell biology techniques, integrated with an engineering approach, to investigate the basic principles underlying the organization of a novel nuclear domain known as the B-body. Through mutational analysis and in vivo expression studies, we demonstrate the interplay between proteins and RNA molecules that contributes to the formation of this domain. However, we were not successful in reconstructing an artificial nuclear domain. Our findings highlight the current limitations in our understanding of nuclear organization and open new directions for future research in this area.