Functions of a novel noncoding RNA family

University Of Colorado At Denver, Aurora CO

Investigators

Abstract

This project seeks to understand how a new family of molecules controls how genes are turned on or off. Unlike most known gene regulators, which are proteins, these regulators are chains of ribonucleotides called noncoding RNAs. These particular ncRNAs were discovered in the model organism C. elegans in earlier work on this project, which also suggested they have functions during C. elegans development. So, this study will reveal new insights into regulatory pathways that are critical to animal development and gene regulation. In addition, the project will develop new methods to detect and count millions of RNA molecules from small amounts of material. These methods could have broad applications including in medical diagnosis, new environmental survey methods, or forensics investigations. This project will also provide scientific training of a graduate student, who will conduct this research as part of their PhD thesis, and will serve as the basis of a research training program for undergraduate students interested in science or science-related careers. Noncoding RNAs (ncRNAs) are rapidly emerging as surprisingly prominent and diverse regulators. However, functions of most ncRNAs are a mystery. Preliminary studies for this project discovered a family of novel ncRNAs that bind Sm rings, relatives of ancient protein complexes found in all domains of life. In eukaryotes, Sm rings are core components of snRNA complexes that catalyze mRNA splicing. However, several studies suggest that Sm rings have a variety of other poorly understood functions. Collectively, these findings suggest that multiple Sm-bound ncRNAs control unknown RNA targets, thereby regulating a variety of processes. This project will explore this idea using the nematode C. elegans as a model system. Targeted gene disruption will be combined with unique high throughput RNA sequencing strategies and established assays to determine how Sm ncRNA mutations alter RNA profiles and other biological functions. Transgene manipulations will test emergent models for how Sm ncRNAs control RNA targets in vivo. This project will reveal functions of novel ncRNAs, which represent a new, poorly understood paradigm of genetic control. Results may transform ideas for the functions of Sm family rings and their ncRNA partners. In addition, this project will help develop new genome scale methods and bioinformatic tools that will have broad applicability to the many other families of ncRNAs emerging from genomes throughout phylogeny.