Samantha Howden
Pronouns: she/her
Research Mentor(s): Sarah Keane
Research Mentor School/College/Department: Biophysics/Chemistry / LSA
Program: UROPF
Session: Session 1 (9:00am – 9:50am)
Authors: Samantha Howden, Sicong Ma, Sarah Keane
Abstract
RNA plays a vital role in cell development. Its dysregulation contributes to the pathogenesis of various diseases such as cancer, making RNA a novel target for drug development. The specific function of an RNA molecule determines its classification as coding or noncoding. MicroRNA (miRNA) – a subset of noncoding RNA – acts as a cell regulator without encoding proteins like its coding counterpart, messenger RNA (mRNA). During the biogenesis pathway to maturation, miRNA is transcribed from DNA sequences into primary miRNA (pri-miRNA). Pre-miRNA is cleaved by the Dicer enzyme to produce mature miRNA, which binds to targeted mRNA in order to downregulate or suppress the expression of protein production. Due to its regulatory role, the level of miRNA in the cell needs to be strictly maintained. Dysregulation of specific miRNA is closely associated with the development of cancerous cells, where abnormal expression of miRNA genes results in the expression of proteins that encourage cell growth. Therefore, it is favorable to prevent the generation of dysregulated mature miRNA. Antisense oligonucleotides (ASOs) are short, single-stranded fragments of DNA or RNA that can inhibit the biogenesis of dysfunctional miRNA. ASOs bind to targeted miRNA through complementary base-pairing in order to control the expression of dysregulated mature miRNA in the cell, which is crucial to inhibiting protein production in cancer cells. Traditional methods using ASOs to target mature miRNA may cause cell toxicity by occupying the Argonaute protein, which is essential for all miRNA functions. We are focused on using a novel method that targets pre-miRNA to minimize the level of mature dysregulated miRNA at an earlier stage of the miRNA biogenesis pathway.
