Development of a Functional RNA-Identifying Computational Pipeline and its Application to SARS-CoV-2
Open Access
Author:
Forstmeier, Peter
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Philip C Bevilacqua, Thesis Supervisor Teh-Hui Kao, Thesis Honors Advisor
Keywords:
SARS-CoV-2 RNA pseudoknots SNPs RNA structure conservation frameshifting element FSE
Abstract:
SARS-CoV-2, the virus that causes COVID-19, is a positive-sense RNA virus with a known regulatory functional RNA structure – structures which have a strong secondary structure and typically a pseudoknot. The functional RNA found in SARS-CoV-2 is the frameshifting element (FSE), which promotes (–1) ribosomal frameshifting. Because they are functional, such RNAs are therapeutic targets and can potentially be disrupted by small molecules or antisense oligonucleotides. Identification of novel functional RNAs in SARS-CoV-2 could open new therapeutic routes. Here we introduce the Functional RNA Identification (FRID) pipeline to identify putative functional RNAs. The guiding principle of the pipeline is that functional RNAs will experience high conservation of sequence, secondary structure, and pseudoknots in the presence of single nucleotide polymorphisms (SNPs) to maintain function. Using the FRID pipeline, thousands of viral genomic isolates were analyzed to assess the presence and conservation levels of putative functional RNAs in SARS-CoV-2. We found seven candidate functional RNAs with this method along with several structural mutations in the FSE. In addition to SARS-CoV-2, the FRID pipeline is broadly applicable and can be applied to RNA genomes or transcriptomes from other organisms.
