RNA key to regulating gene expression across generations

Dissected germ lines from the model organism C. elegans stained for DNA (red) and a marker for areas where gene transcription is repressed (green).
Dissected germ lines from the model organism C. elegans stained for DNA (red) and a marker for areas where gene transcription is repressed (green).

A collaboration led by Monash Biomedicine Discovery Institute (BDI) researcher Dr Peter Boag has found a new player in a pathway that helps to maintain normal genome organisation between generations. Understanding the molecular mechanisms of how small ribonucleic acid (RNA) pathways influence development of progeny over generations is now one of the key questions in RNA biology.

Most people know that deoxyribonucleic acid (DNA) contains the blueprint for life. But what is becoming increasingly clear, is, that how DNA is packaged plays an important role in regulating gene expression.

Small RNAs are now emerging as key molecules to help organise the landscape of gene expression in germ cells (reproductive cells). This work, published late last year in the journal eLife, identified an RNA-binding protein that is required for the normal function of a class of small regulatory RNAs that are critical for maintaining genome integrity in germ cells.

This protein helps the regulatory RNA to define which genes should be expressed and which need to be repressed. When this small RNA pathway is disrupted, defects such as chromosome segregation and DNA packaging are impacted.

This type of stochastic behaviour means the trans-generational changes are happening over time. The researchers observed the onset of sterility over seven to ten generations in animal models.

“This work reveals the complex interactions between small RNA pathways and the proteins that regulate their production and function," Dr Boag said.

“It highlights the broad impact of understanding how small RNAs are critical to survival of a species,” he said.

The study was five years in the making, and represents major local and international collaborations between Dr Boag and Dr Jackie Wilce’s laboratories at Monash, the University of Toronto and the University of Massachusetts.

Read the full paper in eLife titled The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. elegans.

Monash is home to Australia's largest network of RNA and mRNA researchers. Keep up to date with our work on life-saving vaccines and therapeutic treatments on our Monash RNA webpage.


About the Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.