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.

ENTPD3 marks mature stem cell derived beta cells formed by self-aggregation in vitro

August 11, 2021

Fiona M Docherty, Kent A Riemondy, Roberto Castro-Gutierrez, JaeAnn M Dwulet, Ali H Shilleh, Maria S Hansen, Shane P M Williams, Lucas H Armitage, Katherine E Santostefano, Mark A Wallet, Clayton E Mathews, Taylor M Triolo, Richard K P Benninger, Holger A Russ

Stem cell derived beta-like cells (sBC) carry the promise of providing an abundant source of insulin-producing cells for use in cell replacement therapy for patients with diabetes, potentially allowing widespread implementation of a practical cure. To achieve their clinical promise, sBC need to function comparably to mature adult beta cells, but as yet they display varying degrees of maturity. Indeed, detailed knowledge of the events resulting in human beta cell maturation remains obscure. Complete Abstract

Srsf3 mediates alternative RNA splicing downstream of PDGFRα signaling in the facial mesenchyme

July 15, 2021

Brenna J C Dennison, Eric D Larson, Rui Fu, Julia Mo, Katherine A Fantauzzo

Signaling through the platelet-derived growth factor receptor alpha (PDGFRα) is crucial for mammalian craniofacial development, although the mechanisms by which the activity of downstream intracellular effectors is regulated to mediate gene expression changes have not been defined. We find that the RNA-binding protein Srsf3 is phosphorylated at Akt consensus sites downstream of PI3K-mediated PDGFRα signaling in mouse palatal mesenchyme cells, leading to its nuclear translocation. Complete Abstract

LABRAT reveals association of alternative polyadenylation with transcript localization, RNA binding protein expression, transcription speed, and cancer survival

June 26, 2021

Raeann Goering, Krysta L Engel, Austin E Gillen, Nova Fong, David L Bentley, J Matthew Taliaferro  

The sequence content of the 3' UTRs of many mRNA transcripts is regulated through alternative polyadenylation (APA). The study of this process using RNAseq data, though, has been historically challenging. Complete Abstract

Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication

June 16, 2021

Benjamin M Akiyama, Monica E Graham, Zoe O Donoghue, J David Beckham, Jeffrey S Kieft  

Mosquito-borne flaviviruses (MBFVs) including dengue, West Nile, yellow fever, and Zika viruses have an RNA genome encoding one open reading frame flanked by 5' and 3' untranslated regions (UTRs). The 3' UTRs of MBFVs contain regions of high sequence conservation in structured RNA elements known as dumbbells (DBs). Complete Abstract

RNA-binding proteins regulate aldosterone homeostasis in human steroidogenic cells

June 1, 2021

Rui Fu, Kimberly Wellman, Amber Baldwin, Juilee Rege, Kathryn Walters, Antje Hirsekorn, Kent Riemondy, William E Rainey and Neelanjan Mukherjee

Angiotensin II (AngII) stimulates adrenocortical cells to produce aldosterone, a master regulator of blood pressure. Despite extensive characterization of the transcriptional and enzymatic control of adrenocortical steroidogenesis, there are still major gaps in the precise regulation of AII-induced gene expression kinetics. Complete Abstract

More Research Highlights