# Biophysics of Regulatory RNAs and RNPs

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $382,588

## Abstract

Project Summary
Non-coding RNAs are key regulators of diverse biological processes in eukaryotes. MicroRNAs are a family of
small non-coding RNAs that post-transcriptionally regulate gene expression in a sequence-dependent manner.
Approximately 1,000 human microRNAs appear to control the expression of more than half of all human
messenger RNAs. Deviations from homeostatic microRNA expression levels, either reduced or enhanced
expression, have been linked to cancers, diabetes, heart and neurodegenerative diseases, among others. To
maintain proper microRNA expression levels, eukaryotic cells must tightly control the enzymatic processing of
primary and precursor microRNA elements. However, the molecular determinants underlying this strict regulation
of microRNA biogenesis are not fully understood. In this proposal we will explore both cis (RNA structure) and
trans (protein binding partners) regulators of microRNAs biogenesis. In Research Area 1, we will explore the
post-transcriptional regulation of members of the let-7 family of microRNAs. The processing of approximately
half of the let-7 microRNAs is mediated by a protein partner, Lin28. The other members of this family are
regulated by other, often unknown factors. We will determine the extent to which RNA modification, RNA
structure, and RNA dynamics can serve as regulatory triggers to control the processing of these other family
members. In Research Area 2, we will examine the differential processing of oncomiR-1, a polycistronic primary
microRNA that is enriched in many cancers. We will conduct in cell chemical probing studies, identify associated
cellular proteins, and elucidate a structural switch that controls processing of a subdomain. Our long-term goal
is to determine the tertiary structure of oncomiR-1 alone and in complex with regulatory proteins. Collectively,
these studies will help elucidate the molecular determinants underlying the highly-regulated production of
microRNAs. RNA structures remain underdetermined relative to proteins, leading to an asymmetry in our
mechanistic understanding of RNA folding and function. We expect that the methodology and approach
developed in these studies will be broadly applicable to studies of other regulatory RNAs and protein-RNA
complexes. This enhanced structural insight will inform on how RNA structure can directly regulate biological
activity and will pave the way for the development of novel RNA-targeted therapeutics.

## Key facts

- **NIH application ID:** 10226281
- **Project number:** 5R35GM138279-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Sarah Courtney Keane
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,588
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226281

## Citation

> US National Institutes of Health, RePORTER application 10226281, Biophysics of Regulatory RNAs and RNPs (5R35GM138279-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10226281. Licensed CC0.

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