# Structure, function, and dynamics of viral RNAs and RNA-containing complexes

> **NIH NIH R35** · UNIVERSITY OF COLORADO DENVER · 2021 · $605,644

## Abstract

PROJECT SUMMARY
Eukaryotic cells use diverse mechanisms to regulate translation, many of which depend on
structured RNA elements that interact directly with the protein synthesis machinery. This
ubiquitous and powerful strategy for regulating gene expression is also adopted by viral RNAs,
which must use the same biological machinery as cellular RNAs. Despite their importance, the
detailed mechanisms that underlie both cellular and viral RNA structure-dependent translational
control are poorly understood. To address this gap, we propose to build on our previous
discoveries of internal ribosome entry site (IRES) RNA function by studying two different but
related classes of viral RNAs that interface directly with the cellular translation machinery. The
first comprises a diverse class of viral RNAs called tRNA-like structures (TLSs) that mimic tRNAs
in mysterious ways and use this to bind a variety of cellular proteins; in so doing they enhance
translation by unknown means. As new putative tRNA mimics are being discovered, this work
promises insight of broad applicability. The second are termination upstream ribosome binding
sites (TURBS) RNAs, which exist at the interface between two open reading frames where they
drive ribosome reinitiation using unknown RNA structure. Evidence suggests that RNA sequence
and structure can play an important role in ribosome reinitiation, thus studies of these viral TURBS
promise to reveal foundational principles of this process. For these studies, we propose a
‘structure-forward’ strategy that exploits our substantial expertise in three-dimensional RNA
structure determination, coupled with biochemistry to link structure with function and develop
detailed new mechanistic models. In addition, we will use our structural discoveries to guide novel
bioinformatics searches aimed at finding new versions of these structured elements in both
cellular and viral RNAs. We anticipate that our work will inspire new questions about the nature,
diversity, distribution, and power of RNA structure-dependent control of translation, suggest new
systems to study, and help further understand broad underlying principles.

## Key facts

- **NIH application ID:** 10204550
- **Project number:** 2R35GM118070-06
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jeffrey S Kieft
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $605,644
- **Award type:** 2
- **Project period:** 2016-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10204550

## Citation

> US National Institutes of Health, RePORTER application 10204550, Structure, function, and dynamics of viral RNAs and RNA-containing complexes (2R35GM118070-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10204550. Licensed CC0.

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