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.

Alternative RNA Structures Formed During Transcription Depend on Elongation Rate and Modify RNA Processing

February 24, 2021

Tassa Saldi, Kent Riemondy, Benjamin Erickson, and David L. Bentley

Most RNA processing occurs co-transcriptionally. We interrogated nascent pol II transcripts by chemical and enzymatic probing and determined how the “nascent RNA structureome” relates to splicing, A-I editing and transcription speed. RNA folding within introns and steep structural transitions at splice sites are associated with efficient co-transcriptional splicing. Complete Abstract

Qualitative Differences Between the IFNα Subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis

October 16, 2020

Kejun Guo, Guannan Shen, Jon Kibbie, Tania Gonzalez, Stephanie M Dillon, Harry A Smith, Emily H Cooper, Kerry Lavender, Kim J Hasenkrug, Kathrin Sutter, Ulf Dittmer, Miranda Kroehl, Katerina Kechris, Cara C Wilson and Mario L Santiago

The Type I Interferons (IFN-Is) are innate antiviral cytokines that include 12 different IFNα subtypes and IFNβ that signal through the IFN-I receptor (IFNAR), inducing hundreds of IFN-stimulated genes (ISGs) that comprise the 'interferome'.  Complete Abstract

The Crystal Structure of a Polerovirus Exoribonuclease-Resistant RNA Shows How Diverse Sequences are Integrated into a Conserved Fold

August 26, 2020

Anna-Lena Steckelberg, Quentin Vicens, David A. Costantino, Jay C. Nix and Jeffrey S. Kieft

Exoribonuclease-resistant RNAs (xrRNAs) are discrete elements that block the progression of 5′ to 3′ exoribonucleases using specifically folded RNA structures. A recently discovered class of xrRNA is widespread in several genera of plant-infecting viruses, within both...  Complete Abstract

JMJD5 couples with CDK9 to release the paused RNA polymerase II

August 18, 2020

Haolin Liu, Srinivas Ramachandran, Nova Fong, Tzu Phang, Schuyler Lee, Pirooz Parsa, Xinjian Liu, Laura Harmacek, Thomas Danhorn, Tengyao Song, Sangphil Oh, Qianqian Zhang, Zhongzhou Chen, Qian Zhang, Ting-Hui Tu, Carrie Happoldt, Brian O'Conner, Ralf Janknecht, Chuan-Yuan Li, Philippa Marrack, John Kappler, Sonia Leach and Gongyi Zhang

More than 30% of genes in higher eukaryotes are regulated by RNA polymerase II (Pol II) promoter proximal pausing. Pausing is released by the positive transcription elongation factor complex (P-TEFb).  Complete Abstract

Single-Cell RNA Sequencing of Childhood Ependymoma Reveals Neoplastic Cell Subpopulations that Impact Molecular Classification and Etiology

August 11, 2020

Austin E Gillen, Kent A Riemondy, Vladimir Amani, Andrea M Griesinger, Ahmed Gilani, Sujatha Venkataraman, Krishna Madhavan, Eric Prince, Bridget Sanford, Todd C Hankinson, Michael H Handler, Rajeev Vibhakar, Ken L Jones, Siddhartha Mitra, Jay R Hesselberth, Nicholas K Foreman and Andrew M Donson

Ependymoma (EPN) is a brain tumor commonly presenting in childhood that remains fatal in most children. Intra-tumoral cellular heterogeneity in bulk-tumor samples significantly confounds our understanding of EPN biology, impeding development of effective therapy. We, therefore, use single-cell RNA sequencing, histology, and deconvolution to catalog cellular heterogeneity of the major childhood EPN subgroups.  Complete Abstract

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