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Research



The objective of the RNA Bioscience Initiative is to understand the role of RNA in biology, engage in collaborative research, create a fluid pipeline from basic science to clinical diagnostics and therapeutics, and train the next generation of RNA researchers.

Investigators on the CU Anschutz campus have already made important discoveries in the field, covering RNA structure-function, RNA biogenesis, mechanisms of regulation by non-coding RNAs, non-coding RNAs in disease, diagnostics, and therapeutics, cutting-edge RNA technologies and advanced genome-wide computational methods.

The RNA Bioscience Initiative continues to make substantial and sustained contributions to four major research areas:

Highlights

A brief look at the latest discoveries from RBI faculty and trainees.



Lucas

Two Conserved Phenylalanine Residues in the E1 Fusion Loop of Alphaviruses Are Essential for Viral Infectivity

April 13, 2022

Cormac J Lucas, Bennett J Davenport, Kathryn S Carpentier, Alex N Tinega, Thomas E Morrison

Alphaviruses infect cells by a low pH-dependent fusion reaction between viral and host cell membranes that is mediated by the viral E1 glycoprotein. Most reported alphavirus E1 sequences include two phenylalanines (F87 and F95) in the fusion loop, yet the role of these residues in viral infectivity remains to be defined. Following introduction of wild type (WT), E1-F87A, and E1-F95A chikungunya virus (CHIKV) RNA genomes into cells... Complete Abstract

 


Davis- February 2022

Small RNA pathways in the nematode Ascaris in the absence of piRNA

February 11, 2022

Maxim V. Zagoskin, Jianbin Wang, Ashley T. Neff, Giovana M. B. Veronezi, Richard E. Davis

Small RNA pathways play key and diverse regulatory roles in C. elegans, but our under- standing of their conservation and contributions in other nematodes is limited. We analyzed small RNA pathways in the divergent parasitic nematode Ascaris. Ascaris has ten Argonautes with five worm-specific Argonautes (WAGOs) that associate with secondary 5’-triphosphate 22-24G-RNAs. These small RNAs target repetitive sequences or mature mRNAs and are similar to the C. elegans...

Complete Abstract

 


Bilodeau

Precise gene models using long-read sequencing reveal a unique poly(A) signal in Giardia lamblia

February 2, 2022

Danielle Y Bilodeau, Ryan M Sheridan, Balu Balan, Aaron R Jex, Olivia S Rissland

During pre-mRNA processing, the poly(A) signal is recognized by a protein complex that ensures precise cleavage and polyadenylation of the nascent transcript. The location of this cleavage event establishes the length and sequence of the 3' UTR of an mRNA, thus... Complete Abstract

 


Ankora

The role of alternative polyadenylation in the regulation of subcellular RNA localization

January 14, 2022

Ankita Arora, Raeann Goering, Hei Yong G Lo, Joelle Lo, Charlie Moffatt, J Matthew Taliaferro

 

Alternative polyadenylation (APA) is a widespread and conserved regulatory mechanism that generates diverse 3' ends on mRNA. APA patterns are often tissue specific and play an important role in cellular processes such as cell proliferation, differentiation, and response to stress. Many APA sites are found in 3' UTRs, generating mRNA isoforms with different 3' UTR contents. 

These alternate 3' UTR isoforms can change how the transcript is regulated, affecting its stability and translation. Since the subcellular localization of a transcript is often regulated by 3' UTR…

Complete Abstract

 


Kieft- Nov 2021

A viral RNA hijacks host machinery using dynamic conformational changes of a tRNA-like structure

November 19, 2021

Steve L Bonilla, Madeline E Sherlock, Andrea MacFadden, Jeffrey S Kieft

 

Viruses require multifunctional structured RNAs to hijack their host’s biochemistry, but their mechanisms can be obscured by the difficulty of solving conformationally dynamic RNA structures. Using cryo–electron microscopy (cryo-EM), we visualized the structure of the mysterious viral transfer RNA (tRNA)–like structure (TLS) from the brome mosaic virus, which affects replication, translation, and genome encapsidation. Structures in isolation and those bound to tyrosyl-tRNA synthetase (TyrRS) show...  Complete Abstract

 


Morrison- Oct 2021

MARCO+ lymphatic endothelial cells sequester arthritogenic alphaviruses to limit viremia and viral dissemination

October 7, 2021

Kathryn S Carpentier, Ryan M Sheridan, Cormac J Lucas, Bennett J Davenport, Frances S Li, Erin D Lucas, Mary K McCarthy, Glennys V Reynoso, Nicholas A May, Beth A J Tamburini, Jay R Hesselberth, Heather D Hickman, Thomas E Morrison

 

Viremia in the vertebrate host is a major determinant of arboviral reservoir competency, transmission efficiency, and disease severity. However, immune mechanisms that control arboviral viremia are poorly defined. Here, we identify critical roles for the scavenger receptor MARCO in controlling viremia during arthritogenic alphavirus infections in mice. Following subcutaneous inoculation, arthritogenic alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic endothelial cells (LECs) in the draining lymph node (dLN), limiting... Complete Abstract

 


Pearson- October 2021

The SON RNA splicing factor is required for intracellular trafficking structures that promote centriole assembly and ciliogenesis

October 1, 2021

Alexander J Stemm-Wolf, Eileen T O'Toole, Ryan M Sheridan, Jacob T Morgan, Chad G Pearson

 

Control of centrosome assembly is critical for cell division, intracellular trafficking, and cilia. Regulation of centrosome number occurs through the precise duplication of centrioles that reside in centrosomes. Here we explored transcriptional control of centriole assembly and find that the RNA splicing factor SON is specifically required for completing procentriole assembly. Complete Abstract

 


Mukherjee- September 2021

Transcriptomic Response Dynamics of Human Primary and Immortalized Adrenocortical Cells to Steroidogenic Stimuli

 

September 9, 2021

 

Kimberly Wellman, Rui Fu, Amber Baldwin, Juilee Rege, Elisabeth Murphy, William E Rainey, Neelanjan Mukherjee

 

Adrenal steroid hormone production is a dynamic process stimulated by adrenocorticotropic hormone (ACTH) and angiotensin II (AngII). These ligands initialize a rapid and robust gene expression response required for steroidogenesis. Here, we compare the predominant human immortalized cell line model, H295R cell, with primary cultures of adult adrenocortical cells derived... Complete Abstract